Antithrombotic treatment in elderly patients with atrial fibrillation

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Rodríguez Calvín, A. Zapatero Gaviria, M.D. Martín Ríos" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Rodríguez Calvín" ] 1 => array:2 [ "nombre" => "A." 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"apellidos" => "Mostaza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "h" "identificador" => "aff0040" ] ] ] 8 => array:1 [ "colaborador" => "on behalf of Grupo de Trabajo de Riesgo Vascular de la SEMI" ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Hospital Universitario de La Princesa, Grupo de Riesgo Vascular de la SEMI, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Clinic de Barcelona, Grupo de Riesgo Vascular de la SEMI, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Vega Baja de Orihuela, Grupo de Riesgo Vascular de la SEMI, Orihuela, Alicante, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Royo Villanova, Grupo de Riesgo Vascular de la SEMI, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Universitari de Bellvitge, Grupo de Riesgo Vascular de la SEMI, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Complexo Hospitalario Universitario de Santiago, Grupo de Riesgo Vascular de la SEMI, Santiago de Compostela, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital Virgen del Camino, Grupo de Riesgo Vascular de la SEMI, Pamplona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Carlos III, Grupo de Riesgo Vascular de la SEMI, Madrid, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento antitrombótico en el paciente anciano con fibrilación auricular" ] ] "textoCompleto" => "Case reportAn 83-year-old man, with arterial hypertension and diabetes, experienced a hip fracture 2 months ago due to an accidental fall, which was treated with a total hip prosthesis. The patient was treated with 50mg/day of losartan, 5mg/day of amlodipine and 850mg/day of metformin.During a routine examination, the attending physician detected atrial fibrillation of uncertain origin. The patient was asymptomatic from a cardiology standpoint. The physical examination was anodyne, although arrhythmia was detected in the auscultation.Due to the recent fall, the decision was made to anticoagulate the patient with acetylsalicylic acid (100mg/day). Three months later, the patient was admitted to the hospital with a stroke.The clinical problemEpidemiological aspectsAtrial fibrillation (AF) is the most common type of arrhythmia in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0275">1</a> The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study, conducted in the United States, observed that AF affects approximately 1% of the general population, although this percentage increases with age from 0.1% in participants younger than 55 years to 9% in those participants aged 80 years or more.<a class="elsevierStyleCrossRef" href="#bib0280">2</a> The same trend has been observed in Europe; it has been estimated that the prevalence of AF is less than 1% in participants aged 55–59 years and approximately 18% in those who are at least 85 years of age.<a class="elsevierStyleCrossRef" href="#bib0285">3</a> The VAL-FAAP study analyzed approximately 120,000 participants treated in primary care in Spain. The prevalence of AF was 6.1%, a figure that increased with age from somewhat less than 1% in participants younger than 50 years to 17.6% for those 80 years or older.<a class="elsevierStyleCrossRef" href="#bib0290">4</a> In the Observation of Atrial Fibrillation and Coronary Disease in Spain (Observación de Fibrilación Auricular y Enfermedad Coronaria en España, OFRECE) study that analyzed participants 40 years of age and older treated in primary care, the prevalence of AF was 4.4% and progressively increased starting at 60 years of age, reaching 17.7% in those older than 80 years.<a class="elsevierStyleCrossRef" href="#bib0295">5</a> In the DARIOS study that analyzed 6 population-based studies, the prevalence of AF was 1.5%, a figure that increased with the age, up to 6.3% in those older than 75 years.<a class="elsevierStyleCrossRef" href="#bib0300">6</a> Data from the ESFINGE study show that a third of patients older than 70 years hospitalized in the national departments of internal medicine have AF.<a class="elsevierStyleCrossRef" href="#bib0305">7</a>The prevalence of AF not only increases with age but also with the presence of other associated comorbidities, such as ischemic heart disease and heart failure, conditions that are also more prevalent in advanced ages.<a class="elsevierStyleCrossRefs" href="#bib0310">8,9</a> Due to the progressive aging of the population, both the prevalence and incidence of AF has increased markedly in recent years.<a class="elsevierStyleCrossRefs" href="#bib0275">1,10</a>AF increases the risk of stroke by up to 5-fold. More than 15% of stroke episodes are due to AF (36% in individuals older than 80 years).<a class="elsevierStyleCrossRef" href="#bib0315">9</a> Additionally, stroke associated with AF, when compared with stroke unrelated to AF, has higher morbidity and mortality and causes more sequela and hospitalizations, especially in the elderly.<a class="elsevierStyleCrossRefs" href="#bib0325">11–14</a>In the elderly population, the treatment objectives for patients with AF should be focused on preventing complications related to the presence of this arrhythmia, especially stroke, as well as on improving quality of life.<a class="elsevierStyleCrossRef" href="#bib0330">12</a> In this context, anticoagulation plays a fundamental role. However, it is particularly important with the elderly population to balance the risk of both stroke and bleeding, given that both are increased in these patients.<a class="elsevierStyleCrossRef" href="#bib0330">12</a>The objective of this update was to review the specific comments by the clinical practice guidelines on antithrombotic treatment in elderly patients with nonvalvular AF (NVAF). It is important to emphasize that the definition of the elderly patient has changed over time. Although in the past elderly patients were considered those aged 65 years or older, the various current clinical practice guidelines and the studies performed with direct oral anticoagulants have raised this cutoff to 75 years.Clinical profile of elderly patients with atrial fibrillationThe management of elderly patients with AF is complex due to, among other things, their considerable number of comorbidities, which often result in polymedication. Thus, it has been observed among patients with hypertension and chronic ischemic heart disease that those with AF are older and more often present diabetes, left ventricular hypertrophy, heart failure, peripheral arterial disease, renal failure and stroke, when compared with those in sinus rhythm.<a class="elsevierStyleCrossRef" href="#bib0315">9</a> Moreover, it appears that patients with AF have an increased risk of dementia, particularly those with a history of stroke.<a class="elsevierStyleCrossRef" href="#bib0345">15</a> In fact, there are various peculiarities in the elderly that confer a condition of frailty. Physical and mental abnormalities are common, especially cognitive and mood disorders, risk of falls, malnutrition and social dependence, which have a significant impact on the management of these patients.<a class="elsevierStyleCrossRef" href="#bib0330">12</a>Advanced age is itself an independent predictor of both stroke and mortality after the stroke, as well as the risk of bleeding.<a class="elsevierStyleCrossRefs" href="#bib0350">16–20</a> This aspect is considered in the risk scales. On the CHADS2 scale, an age ≥75 years scores 1 point, reinforcing the increase in risk with increasing age. For the CHA2DS2-VASc scale, an age between 65 and 74 years is awarded 1 point, increasing to 2 for ages >75 years. In terms of the risk of bleeding, an age >65 years scores 1 point on the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scale.<a class="elsevierStyleCrossRefs" href="#bib0355">17–20</a>Consequently, taking into account the above described determinants, it is especially important for elderly patients to not only balance the risk of stroke with that of hemorrhage but also to assess the possibility of properly taking medication, the availability of a caregiver, the social support, etc.<a class="elsevierStyleCrossRefs" href="#bib0330">12,21</a> In principle, except when the patient has a high risk of bleeding, the considerable majority of elderly patients with NVAF should undergo permanent anticoagulation. Nevertheless, the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study found no evidence that, when compared with acetylsalicylic acid, anticoagulation provided clinically relevant protection against cognitive impairment in patients after 33 months of treatment.<a class="elsevierStyleCrossRef" href="#bib0380">22</a> A decision algorithm has recently been proposed for better profiling geriatric patients with NVAF who will most benefit from treatment with vitamin K antagonists. The algorithm includes 6 items (previous bleeding with vitamin K antagonists, degree of autonomy, mini mental state examination [MMSE] score, risk of falls and comorbidity index). Each variable has a score (0, 0.5 and 1 point) according to the intensity (mild, moderate or high).<a class="elsevierStyleCrossRef" href="#bib0385">23</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the peculiarities of AF in this age group.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Strategies and evidenceAnticoagulation with vitamin K antagonists for elderly patientsTraditionally, anticoagulation for patients with AF has been performed with vitamin K antagonists. In fact, it has been shown that anticoagulant therapy with vitamin K antagonists is an effective treatment for the prevention of stroke and thromboembolism when compared with antiplatelet agents, including acetylsalicylic acid.<a class="elsevierStyleCrossRefs" href="#bib0390">24,25</a>Anticoagulant treatment with vitamin K antagonists is also beneficial for the elderly population. The BAFTA study compared warfarin treatment with acetylsalicylic acid treatment (75mg/day), with approximately 1000 participants 75 years of age or older with AF who were followed-up for a mean time of 2.7 years. The warfarin treatment was associated with a significant reduction (52%) in the risk of fatal or debilitating stroke, intracranial hemorrhage and clinically significant arterial embolism, with no significant differences in the risk of extracranial hemorrhage.<a class="elsevierStyleCrossRef" href="#bib0400">26</a> Subsequent studies have confirmed the benefits of anticoagulation in this population.<a class="elsevierStyleCrossRefs" href="#bib0405">27,28</a>Although it is certain that the risk of bleeding is increased in elderly patients,<a class="elsevierStyleCrossRefs" href="#bib0365">19,29</a> permanent anticoagulation is indicated for the majority of elderly patients with AF. However, the reality is that a significant number of patients who have an indication for anticoagulation do not receive it, precisely because of the fear of bleeding.<a class="elsevierStyleCrossRefs" href="#bib0315">9,30–34</a> In a study performed with approximately 600 participants with NVAF, only 34% of the participants were treated with anticoagulation at discharge. This percentage was even lower for the more elderly participants (42% among individuals aged 65–75 years and 29% for those older than 75 years; p<0.001).<a class="elsevierStyleCrossRef" href="#bib0425">31</a> In addition to bleeding, the factors that promote this situation include falls, which should never be an absolute contraindication for anticoagulation. However, given that frequent falls in elderly patients with AF are associated with higher mortality, in the patient group with a lower CHA2DS2-VASc score (e.g., 0–3), the decision to provide anticoagulation therapy to the patient should be made by carefully assessing the risk/benefit ratio.<a class="elsevierStyleCrossRef" href="#bib0445">35</a>Vitamin K antagonists have certain limitations, such as their narrow therapeutic window, variable anticoagulant response, interactions with food and other drugs and a slow start and end of action, which require the implementation of periodic checkups and frequent dosage adjustments (more common in the elderly). These limitations undoubtedly contribute to the underutilization of these drugs in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0290">4</a>Direct oral anticoagulants in elderly patientsDirect oral anticoagulants (dabigatran, rivaroxaban, apixaban and, more recently, edoxaban) have at least a similar efficacy as warfarin in preventing stroke and systemic embolism but have a better safety profile, mainly due to the lower risk of intracranial hemorrhage for patients with NVAF. In addition to having predictable kinetics and a broad therapeutic window, these anticoagulants can be prescribed at a fixed dosage, without the need for periodic checkups.<a class="elsevierStyleCrossRef" href="#bib0450">36</a> Clinical trials specifically designed to assess the safety and efficacy of these drugs in elderly populations have unfortunately not been performed. However, in recent years, various subanalyses have been published on the safety and efficacy of direct oral anticoagulants by age.In the RE-LY study that compared dabigatran to warfarin, both dabigatran dosages had a lower risk of both intracranial and extracranial bleeding in the participants younger than 75 years. The patients aged 75 years or older had less frequent intracranial bleeding, but the extracranial bleeding was equal or more frequent.<a class="elsevierStyleCrossRef" href="#bib0455">37</a> Given that the elimination of dabigatran is performed mainly by the kidneys and that the elderly frequently have renal failure, close monitoring of renal function is important for these patients.<a class="elsevierStyleCrossRef" href="#bib0460">38</a> Although the standard recommended dosage for dabigatran is 150mg/12h, it is recommended that the dosage be reduced to 110mg/12h for patients aged 80 years or older. For patients aged 75–80 years or with moderate renal failure, the dosage is selected depending on the risk of stroke/bleeding. In the ROCKET-AF study (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) that compared warfarin to rivaroxaban, the efficacy (risk of stroke and systemic embolism) and safety (risk of major bleeding) of rivaroxaban were consistent with the overall study results, regardless of age.<a class="elsevierStyleCrossRef" href="#bib0465">39</a> In the Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE) study, apixaban was more effective in reducing the risk of stroke and mortality, with fewer major bleeding episodes, total bleeding episodes and intracranial bleeding episodes, regardless of age, including with patients aged 80 years or older.<a class="elsevierStyleCrossRef" href="#bib0470">40</a> In a recent meta-analyses of patients aged 75 years or older enrolled in clinical trials performed with rivaroxaban, apixaban and dabigatran, the direct oral anticoagulants as a whole were more effective than standard treatment in the prevention of stroke and systemic embolism.<a class="elsevierStyleCrossRef" href="#bib0475">41</a> In the ENGAGE AF-TIMI 48 study, both edoxaban dosages were noninferior to warfarin with respect to preventing stroke and systemic embolism but had fewer major bleeding episodes, regardless of age (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0480">42</a><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows how the dosage adjustments for dabigatran, rivaroxaban and apixaban should be performed for patients with NVAF, depending on age, renal function and weight.<a class="elsevierStyleCrossRefs" href="#bib0485">43–45</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Controversy and issues to be resolvedDespite the recent proliferation of guidelines that, to various degrees, refer to the elderly, the evidence in this population group is scarce, and there are a number of unresolved issues that are frequently faced by clinicians in their daily practice.A number of these issues are examined below. The major advantage of direct oral anticoagulants is the reduction in intracranial hemorrhage. In addition, there are data from neuroimaging tests (e.g., microinfarctions, leukoaraiosis, and microhemorrhages) that are associated with an increased risk of intracranial hemorrhage, particularly in cases where there is a history of ischemic stroke. Given this, should a brain CT scan/MRI be performed for elderly patients with an indication of anticoagulation, due to their greater risk of bleeding and high prevalence of the previously mentioned lesion? What type of antithrombotic treatment is the treatment of choice for an elderly patient with a history of frequent falls? In what way does cognitive impairment determine the indication and type of antithrombotic treatment in elderly patients with AF? How often and under what circumstances should renal function be monitored in elderly patients undergoing anticoagulation? Under what circumstances is the temporary or definitive withdrawal of anticoagulation recommended for the elderly? How should antithrombotic treatment be managed for patients with a high risk of gastrointestinal bleeding? How does polypharmacy and poorer treatment compliance influence the choice of anticoagulant treatment for the elderly? How should weight and frailty affect the dosage of direct oral anticoagulants in elderly patients? Are there sufficient data on their safety and efficacy to recommend direct oral anticoagulants to very elderly patients? The answers to these questions will probably only be found when sufficient experience in the real world is available.What do the clinical practice guidelines say on this matter?In recent years, various clinical practice guidelines have been published on managing patients with AF. Although the recommendations are generally given regardless of age, a number have specific comments on elderly populations, which we will review below.In 2010, the European Society of Cardiology published guidelines for the management of patients with AF.<a class="elsevierStyleCrossRef" href="#bib0355">17</a> These guidelines dedicate a specific paragraph to elderly populations. Among other issues, the guidelines state that AF is more common the older the patient and provide the clinical characteristics of this population. Furthermore, the guidelines emphasize that a strategy of heart rate control is preferable to rhythm control in the elderly population. For the risk stratification of stroke and bleeding, the guidelines propose the use of the CHA2DS2-VASc and HAS-BLED scales. Unless contraindicated, anticoagulation is recommended. The benefit of antiplatelet treatment is highly limited in this population, given that the risk of major bleeding episodes is very similar to that of anticoagulation, while antiplatelet treatment is much less effective in terms of preventing stroke and cardiovascular events. It has been suggested that an international normalized ratio (INR) range between 1.8 and 2.5 would be safer for the elderly population who undergo anticoagulation with vitamin K antagonists. However, the reality is that this range has not been endorsed by any clinical trial. Cohort studies have suggested an increased risk of stroke with an INR range of 1.5–2.0; therefore, it is recommended that the INR not fall below 2.0. Only RE-LY study data have been published and the European Medicines Agency (EMA, <a href="http://www.ema.europa.eu/">http://www.ema.europa.eu/</a>) has not approved the use of vitamin K in patients with NVAF. However these guidelines recommend the use of vitamin K antagonists, although they make a number of general recommendations on the use of dabigatran (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0355">17</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The update to these guidelines was published in 2012. These guidelines continue to recommend the use of the CHA2DS2-VASc and Has-BLED scales and emphasize the lack of benefit from acetylsalicylic acid. They also comment on the results of 3 clinical trials with direct oral anticoagulants (RE-LY, ROCKET-AF and ARISTOTLE) and the concern regarding its applicability to more elderly populations. For patients aged 80 years and older, the dabigatran dosage to be used is 110mg/12h (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0360">18</a>The proposed guidelines by the American Heart Association and the American Stroke Association for the primary prevention of stroke emphasize the need to control arterial hypertension in the elderly (mainly systolic blood pressure), which, along with appropriate antithrombotic treatment, are essential for preventing the development of stroke in patients with AF. In most elderly patients with stable ischemic heart disease and AF, anticoagulant treatment is sufficient. Moreover, the detection of brain microhemorrhages in MRI could be useful when assessing the safety of antithrombotic treatment in an elderly patient (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0500">46</a>The 2012 Canadian AF guidelines indicate that advanced age (>75years) is considered a risk factor not only for stroke but also for hemorrhage, particularly intracranial. The use of the CHADS2, CHA2DS2-VASc and HAS-BLED scales is recommended. With regard to direct oral anticoagulants, dosage reductions are recommended for patients older than 75 years, especially for those older than 80 and especially with dabigatran. Moreover, all patients with AF undergoing treatment with anticoagulants should undergo periodic monitoring of their renal function at least once a year (more frequently in cases of renal failure) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0505">47</a>The recommendations proposed by the American College of Chest Physicians are not substantially different according to the age. They do however specify that the risk of stroke increases with age, as reflected in the CHADS2 risk stratification scale, as well as the risk of bleeding (older than 65 years on the HAS-BLED scale, older than 75 years on the HEMORR2HAGES scale) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0510">48</a>The guidelines of the European Heart Rhythm Association, which specifically cover the use of direct oral anticoagulants in patients with NVAF, insist on the need for renal function monitoring. That is especially relevant in elderly patients (older than 75 years) or those who are taking dabigatran. For patients with active cancer, vitamin K antagonists or heparins are preferred over direct oral anticoagulants, given the lack of experience with the latter in this context and possibility of interactions with chemotherapy drugs. In the event that antiplatelet therapy is considered necessary in the first year after an acute ischemic episode, the use of low doses of direct oral anticoagulants is considered safer, especially for patients with HAS-BLED scores ≥3. In this context, vitamin K antagonists (INR objective 2–2.5) might be preferable, especially for very elderly populations and for those with renal failure (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0515">49</a>The guidelines of the Spanish Society of Neurology recommend anticoagulation, except when contraindicated, for patients with NVAF and a high risk of stroke (patients older than 75 years). For these patients, both vitamin K antagonists and direct oral anticoagulants may be used. In fact, the guidelines specifically indicate that despite the hemorrhagic risk, oral anticoagulants show a clear benefit in patients older than 85 years who have AF (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0520">50</a>The guidelines of the American College of Cardiology, American Heart Association and Heart Rhythm Society have been recently published. These guidelines have a specific section dedicated to the elderly population that indicates that the prevalence of AF increases with age and that the presence of other comorbidities is more common. Clinicians usually opt for a heart rate control strategy, more so than a rhythm control strategy, especially considering the possibility of the adverse effects of antiarrhythmic agents in this population. The use of the CHA2DS2-VASc scale is recommended, as well as anticoagulation, for patients aged 75 years or older, either with vitamin K antagonists or direct oral anticoagulants, except where contraindicated. Patients’ renal function should be measured before starting treatment with direct oral anticoagulants, as well as subsequently during monitoring at least once a year (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0525">51</a>Similarly, guidelines proposed by a subcommittee of the American Academy of Neurology have been recently published. These guidelines recognize the benefit of anticoagulation in elderly patients (older than 75 years). The main recommendation of these guidelines is that, except where there is recent spontaneous bleeding or intracranial hemorrhage, anticoagulation should be proposed for all elderly patients with NVAF, including patients with mild dementia or occasional falls. However, the benefit of anticoagulation in patients with moderate to severe dementia or with frequent falls is uncertain (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRef" href="#bib0530">52</a>The recent NICE guidelines recommend, on one hand, a heart rate control strategy and, on the other, anticoagulation for those participants with NVAF and a CHA2DS2-VASc score ≥2. Apixaban, dabigatran, rivaroxaban and vitamin K antagonists may be used.<a class="elsevierStyleCrossRef" href="#bib0535">53</a>In summary, the various clinical practice guidelines as a whole recognize that elderly patients with AF are complex patients with numerous comorbidities and who are frequently polymedicated. All elderly patients with AF should (unless contraindicated) undergo permanent anticoagulant treatment, although it is important to assess the risk of bleeding. In terms of the type of oral anticoagulant to use in the elderly population, both vitamin K antagonists and direct oral anticoagulants may be used in these patients. If the latter are used, it is important that renal function be monitored during follow-up, especially when the patient has known renal failure or is taking dabigatran. Unfortunately and despite the fact that the recommendations of the clinical practice guidelines appear clear, a study performed with patients with NVAF in Spain found that 42% of patients did not follow the recommendations of the European Society of Cardiology.<a class="elsevierStyleCrossRef" href="#bib0540">54</a>How should our patient have been evaluated and treated?Before the stroke, this patient already presented a very high risk of thromboembolic complications (CHA2DS2-VASc: 4; 2 points for age; 1 point for hypertension and 1 point for diabetes). The patient should have therefore undergone anticoagulation. The two factors that had the greatest weight for not starting anticoagulation were the history of casual falls and the patient's age, despite the high thromboembolic risk he had, as subsequently happened. The patient underwent anticoagulation after the stroke.In conclusion, the management of NVAF in the elderly is complicated, and, due to the increased risk of thromboembolic complications and hemorrhage, the decision to administer anticoagulation therapy should be individualized. There are still unresolved questions and lack of evidence in this population. Data from observational studies in our standard practice are needed and are important for the decision-making process.FundingEditorial assistance was provided by Content Ed Net and sponsored by Bayer.Conflicts of interestDr. Carmen Suárez has received has received honoraria for lectures and advising from BMS, Pfizer, Boheringher, Bayer and Daichii Sankyo. Dr. Francesc Formiga has received honoraria for lectures and advising from BMS, Pfizer, Boheringher, Bayer and Daichii Sankyo Dr. A pose Reino declares having received honoraria for lectures and advising from BMS, Pfizer, Boheringher and Bayer. The remaining authors declare having no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres468581" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec491222" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres468582" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec491221" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "The clinical problem" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Epidemiological aspects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical profile of elderly patients with atrial fibrillation" ] ] ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Strategies and evidence" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Anticoagulation with vitamin K antagonists for elderly patients" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Direct oral anticoagulants in elderly patients" ] ] ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Controversy and issues to be resolved" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "What do the clinical practice guidelines say on this matter?" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "How should our patient have been evaluated and treated?" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-10-10" "fechaAceptado" => "2014-11-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec491222" "palabras" => array:8 [ 0 => "Elderly" 1 => "Nonvalvular atrial fibrillation" 2 => "Guidelines" 3 => "Vitamin K antagonists" 4 => "Dabigatran" 5 => "Rivaroxaban" 6 => "Apixaban" 7 => "Edoxaban" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec491221" "palabras" => array:8 [ 0 => "Anciano" 1 => "Fibrilación auricular no valvular" 2 => "Guías" 3 => "Antagonistas de la vitamina K" 4 => "Dabigatran" 5 => "Rivaroxaban" 6 => "Apixaban" 7 => "Edoxaban" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Atrial fibrillation (AF) in the elderly is a complex condition due to the high number of frequently associated comorbidities, such as cardiovascular and kidney disease, cognitive disorders, falls and polypharmacy.Except when contraindicated, anticoagulation is necessary for preventing thromboembolic events in this population. Both vitamin K antagonists and direct oral anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this context. Renal function should be closely monitored for this age group when these drugs are used.In recent years, various clinical practice guidelines have been published on patients with AF. The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients. In this update, we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La fibrilación auricular (FA) en el anciano es una entidad compleja debido al elevado número de comorbilidades frecuentemente asociadas, como las enfermedades cardiovasculares y la enfermedad renal, los trastornos cognitivos, las caídas o la polimedicación.Excepto cuanto esté contraindicada, la anticoagulación es necesaria para la prevención de los eventos tromboembólicos en esta población. Tanto los antagonistas de la vitamina K como los anticoagulantes orales de acción directa (dabigatran, rivaroxaban y apixaban) están indicados en este contexto. En este grupo de edad la función renal debe ser estrechamente vigilada cuando se utilizan estos últimos.En los últimos años se han publicado diferentes guías de práctica clínica sobre el paciente con FA. La mayoría de estas guías realizan recomendaciones específicas sobre las características clínicas y el tratamiento en los pacientes ancianos. En esta actualización se revisan los comentarios específicos sobre las recomendaciones referentes al tratamiento antitrombótico en los pacientes ancianos con FA no valvular." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Suárez Fernández C, Camafort M, Cepeda Rodrigo JM, Díez-Manglano J, Formiga F, Pose Reino A, et al. Tratamiento antitrombótico en el paciente anciano con fibrilación auricular. Rev Clin Esp. 2015;215:171–181." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviation: AF, atrial fibrillation.Adapted from: Lubitz et al.,<a class="elsevierStyleCrossRef" href="#bib0275">1</a> Go et al.,<a class="elsevierStyleCrossRef" href="#bib0280">2</a> Heeringa et al.,<a class="elsevierStyleCrossRef" href="#bib0285">3</a> Barrios et al.,<a class="elsevierStyleCrossRef" href="#bib0290">4</a> Gómez-Doblas et al.,<a class="elsevierStyleCrossRef" href="#bib0295">5</a> Baena-Díez et al.,<a class="elsevierStyleCrossRef" href="#bib0300">6</a> López Soto et al.,<a class="elsevierStyleCrossRef" href="#bib0305">7</a> Rodríguez-Mañero et al.,<a class="elsevierStyleCrossRef" href="#bib0310">8</a> Barrios et al.,<a class="elsevierStyleCrossRef" href="#bib0315">9</a> Freedman et al.,<a class="elsevierStyleCrossRef" href="#bib0320">10</a> Mérida-Rodrigo et al.,<a class="elsevierStyleCrossRef" href="#bib0325">11</a> Hanon et al.,<a class="elsevierStyleCrossRef" href="#bib0330">12</a> Rønning et al.,<a class="elsevierStyleCrossRef" href="#bib0350">16</a> Camm et al.,<a class="elsevierStyleCrossRef" href="#bib0355">17</a> Camm et al.,<a class="elsevierStyleCrossRef" href="#bib0360">18</a> Pisters et al.,<a class="elsevierStyleCrossRef" href="#bib0365">19</a> Lip et al.,<a class="elsevierStyleCrossRef" href="#bib0370">20</a> Mant et al.,<a class="elsevierStyleCrossRef" href="#bib0400">26</a> Lip and Lane,<a class="elsevierStyleCrossRef" href="#bib0405">27</a> Siu and Tse,<a class="elsevierStyleCrossRef" href="#bib0410">28</a> Formiga et al.,<a class="elsevierStyleCrossRef" href="#bib0420">30</a> Gage et al.,<a class="elsevierStyleCrossRef" href="#bib0425">31</a> Gao et al.,<a class="elsevierStyleCrossRef" href="#bib0430">32</a> Darnell et al.<a class="elsevierStyleCrossRef" href="#bib0435">33</a> and Fuenzalida et al.<a class="elsevierStyleCrossRef" href="#bib0440">34</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">The prevalence and incidence of AF increase with age. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stroke associated with AF, when compared with stroke unrelated to AF, has increased mortality and morbidity and more sequela, especially in the elderly. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Elderly patients with AF have a higher number of hospitalizations, increased mortality and generate a greater degree of dependence when compared with younger patients. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Elderly patients have a considerable number of comorbidities, which frequently results in polymedication. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">They also have other physical and mental disorders, especially cognitive and mood disorders, risk of falls, malnutrition and social dependence. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">They are frequently underdiagnosed, given that AF often progresses in the elderly asymptomatically or with few symptoms. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Advanced age is an independent predictor of stroke and mortality after stroke, as well as a risk of bleeding. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Except where contraindicated, elderly patients with AF should undergo anticoagulation. However, many are not due to the fear of bleeding. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab725463.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Peculiarities of atrial fibrillation in the elderly patient." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: NVAF, nonvalvular atrial fibrillation; CrCl, creatinine clearance; ITT, intention to treat.Adapted from Eikelboom et al.,<a class="elsevierStyleCrossRef" href="#bib0455">37</a> Halperin et al.,<a class="elsevierStyleCrossRef" href="#bib0465">39</a> Halvorsen et al.,<a class="elsevierStyleCrossRef" href="#bib0470">40</a> and Giugliano et al.<a class="elsevierStyleCrossRef" href="#bib0480">42</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Population/comparator groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">RE-LY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18,113 patients (mean age, 71.5 years; 40.1% ≥75years; mean CHADS2 score, 2.1) with NVAF were randomized to dabigatran 110mg/12h, dabigatran 150mg/12h or warfarin. Mean follow-up, 2.0 years. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">When compared with warfarin, both dabigatran dosages (110mg and 150mg twice daily) presented a lower risk of intracranial and extracranial bleeding in participants younger than 75 years. For participants 75 years or older, intracranial bleeding was less frequent but extracranial was the same or more frequent. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ROCKET-AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14,264 patients with NVAF (mean age, 73 years; 44% ≥75 years; mean CHADS2 score, 3.4) were randomized to rivaroxaban (20mg/day; 15mg if CrCl <50mL/min) in comparison with warfarin. Mean follow-up of 707 days in the ITT analysis; 590 days in the per-protocol analysis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The elderly patients had a greater risk of stroke and major bleeding episodes when compared with the younger patients.The efficacy (risk of stroke and systemic embolism) and safety (risk of major bleeding episodes) of rivaroxaban when compared with warfarin were consistent with the overall results of the study, regardless of age. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ARISTOTLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18,201 patients (mean age, 70 years; 31% ≥75 years; 13% ≥80 years; mean CHADS2 score, 2.1) with NVAF were randomized to apixaban 5mg/12h (or 2.5mg/12h in case ≥2 of the following criteria were met: age ≥80 years, weight ≤60kg, or creatinine level ≥133μmol/L) or warfarin. Mean follow-up, 1.8 years. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Apixaban was more effective in reducing the risk of stroke and mortality, with fewer major bleeding episodes, total bleeding episodes and intracranial bleeding episodes, regardless of age. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ENGAGE AF-TIMI 48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21,105 patients (mean age, 72 years; 40.1% ≥75 years; mean CHADS2 score, 2.8) with NVAF were randomized to edoxaban 30mg/day, edoxaban 60mg/day or warfarin. Mean follow-up, 2.8 years. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Both edoxaban dosages (30 and 60mg/day) were noninferior to warfarin with respect to preventing stroke and systemic embolism but had fewer major bleeding episodes, regardless of age. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab725464.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of the RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF-TIMI 48 studies by age." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: CrCl, creatinine clearance; NVAF, nonvalvular atrial fibrillation.Adapted from: European Medicines Agency (EMA), Pradaxa®<a class="elsevierStyleCrossRef" href="#bib0485">43</a>; European Medicines Agency (EMA), Xarelto®<a class="elsevierStyleCrossRef" href="#bib0490">44</a>; and European Medicines Agency (EMA), Eliquis®<a class="elsevierStyleCrossRef" href="#bib0495">45</a>." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosage adjustment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Dabigatran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Based on age:• 75 years: 150mg/12h• 75–80 years: 150 or 110mg/12h, depending on thrombotic/hemorrhagic risk• ≥80 years: 110mg/12h• Based on renal function:If CrCl ≥50mL/min: dosage adjustment not necessary.• If CrCl is 30–50mL/min: assess 150mg or 110mg/12h, depending on thrombotic/hemorrhagic risk.• If CrCl <30mL/min: contraindicated• Concomitant use of verapamil: 110mg/12h• Based on weight: A dosage adjustment is not necessary, although close follow-up is recommended for patients weighing <50kg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rivaroxaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Based on age: No dosage adjustment required• Based on renal function:• If CrCl ≥50mL/min: recommended dosage is 20mg/day.• If CrCl is 15–49mL/min: recommended dosage is 15mg/day.• If CrCl <15mL/min: not recommended.• Based on weight: No dosage adjustment required \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Apixaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• In general, the recommended dosage is 5mg/12h. The dosage should be reduced to 2.5mg/12h for NVAF and ≥2 of the following criteria: ≥80 years, ≤60kg or serum creatinine level ≥1.5mg/dL.• Based on age: No dosage adjustment required, except for age ≥80 years, weight ≤60kg or creatinine level ≥1.5mg/dL.• Based on renal function:• Dosage adjustments are not required for patients with mild to moderate renal failure.• If creatinine level is ≥1.5mg/dL: recommended dosage is 5mg/12h, except for patients ≥80 years or ≤60kg for whom the dosage should be reduced to 2.5mg/12h.• If CrCl is 15–29mL/min: recommended dosage is 2.5mg/12h.• If CrCl is <15mL/min or on dialysis: not recommended.• Based on weight: No dosage adjustment required, except for age ≥80 years, weight ≤60kg or creatinine level ≥1.5mg/dL. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab725462.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Dosage adjustment of dabigatran, rivaroxaban and apixaban for patients with nonvalvular atrial fibrillation." ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: ESC, European Society of Cardiology; NICE, National Institute for Health and Care Excellence; SEN, Spanish Society of Neurology.Adapted from Camm et al.,<a class="elsevierStyleCrossRef" href="#bib0355">17</a> Camm et al.,<a class="elsevierStyleCrossRef" href="#bib0360">18</a> EMA Pradaxa®,<a class="elsevierStyleCrossRef" href="#bib0485">43</a> EMA Xarelto®,<a class="elsevierStyleCrossRef" href="#bib0490">44</a> EMA Eliquis®,<a class="elsevierStyleCrossRef" href="#bib0495">45</a> Goldstein et al.,<a class="elsevierStyleCrossRef" href="#bib0500">46</a> Skanes et al.,<a class="elsevierStyleCrossRef" href="#bib0505">47</a> You et al.,<a class="elsevierStyleCrossRef" href="#bib0510">48</a> Heidbuchel et al.<a class="elsevierStyleCrossRef" href="#bib0515">49</a> and Fuentes et al.<a class="elsevierStyleCrossRef" href="#bib0520">50</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Guidelines (year of publication) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ESC (2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific section dedicated to the elderly population.Compared with younger patients, the elderly:Are frailer and have more comorbidities.Permanent AF is more common than paroxysmal/persistent AF.Atypical symptoms are more common.They have a greater likelihood of presenting adverse effects from the drugs.They are frequently underdiagnosed.In general, a heart rate control strategy is preferred over a rhythm control strategy.Given that patients older than 75 years with AF have a >4% annual risk of presenting thromboembolic complications, anticoagulation is indicated unless the risk of bleeding is very high (the benefit of antiplatelet therapy is very limited in this population). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">American Heart Association/American Stroke Association (2011) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">To prevent stroke in the elderly, it is essential to control blood pressure (mainly systolic) and have appropriate antithrombotic treatment.The effects of combining antiplatelet with anticoagulant treatment in this population have not been clearly established.In most elderly patients with stable ischemic heart disease and AF, anticoagulant treatment is sufficient.The detection of brain microhemorrhages in MRI could be useful when assessing the safety of antithrombotic treatment in an elderly patient. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ESC (2012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The guidelines continue to recommend the use of the CHA2DS2-VASc and HAS-BLED scales for the risk stratification of stroke and bleeding, respectively.The guidelines emphasize the scarce benefit of aspirin for these patients, with a high risk of bleeding, and that its use should be limited to those patients who reject any type of anticoagulation.There is concern on how to adapt the results of clinical trials with direct oral anticoagulants to the more elderly population, who have numerous comorbidities and are frequently polymedicated, as well as the fact that individuals with severe renal failure were excluded from these studies. This is particularly important with dabigatran. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Canadian Guidelines (2012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The guidelines recommend the use of the CHADS2 and CHA2DS2-VASc scales for the risk stratification of stroke and the HAS-BLED scale for assessing the risk of bleeding.With regard to direct oral anticoagulants, dosage reductions are recommended for patients older than 75 years, especially for those older than 80 and especially with dabigatran.All patients with AF undergoing treatment with anticoagulants should undergo periodic monitoring of their renal function at least once a year. Patients with a glomerular filtration rate of 30–50mL/min need a closer monitoring of their renal function and might require anticoagulant dosage reductions in certain conditions. This is especially important for patients older than 75 years, in whom the risk of bleeding increases significantly. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">American College of Chest Physicians (2012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">There are no substantial differences by age.The guidelines specify that the risk of stroke and bleeding increases with age. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">European Heart Rhythm Association (2013) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific guidelines on direct oral anticoagulants for patients with NVAF.The guidelines insist on the need to monitor renal function (annually, every 6 months and every 3 months for creatinine clearance levels ≥60, 30–60 and <30mL/min, respectively). This is especially relevant in elderly patients (older than 75 years) or those who are taking dabigatran.For patients with concomitant active cancer who need anticoagulation, vitamin K antagonists or heparins are preferred over direct oral anticoagulants.In the event that antiplatelet therapy is considered necessary in the first year after an acute ischemic episode, the use of low doses of direct oral anticoagulants is considered safer, especially for patients with HAS-BLED scores ≥3. In this context, vitamin K antagonists (INR objective 2–2.5) might be preferable, especially for very elderly populations and for those with renal failure. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SEN (2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The guidelines recommend anticoagulation for patients with NVAF and a high risk of stroke (CHADS2 score ≥2 or CHA2DS2-VASc score ≥1). Therefore, all patients older than 75 years should undergo anticoagulation, except where contraindicated.Vitamin K antagonists and direct oral anticoagulants may be used. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">American College of Cardiology/American Heart Association/Heart Rhythm Society (2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific section dedicated to the elderly population.Elderly patients have a greater possibility of presenting other comorbidities, which can influence the approach.Given that AF symptoms in these patients are usually scarce, a heart rate control strategy is usually selected.The guidelines recommend the use of the CHA2DS2-VASc scale for the risk stratification of stroke in patients with NVAF, recommending anticoagulation (either with vitamin K antagonists or direct oral anticoagulants) for patients with a CHA2DS2-VASc score ≥2.Patients’ renal function should be measured before starting treatment with direct oral anticoagulants, as well as subsequently at least once a year. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">American Academy of Neurology (2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">These guidelines recognize the benefit of anticoagulation in elderly patients (older than 75 years). However, many physicians do not use them because they believe that there is a very high risk of bleeding.Except where there is recent spontaneous bleeding or intracranial hemorrhage, anticoagulation should be proposed for all elderly patients with NVAF, including patients with mild dementia or occasional falls.The benefit of anticoagulation in patients with moderate to severe dementia or with frequent falls is uncertain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">NICE (2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In patients aged 75 years or older, the prevalence of AF is high (almost 15%).A heart rate control strategy is recommended over a rhythm control strategy.The use of anticoagulation is recommended for patients with a CHA2DS2-VASc score ≥2.For patients aged 75 years or older, anticoagulation (with apixaban, dabigatran, rivaroxaban or the vitamin K antagonists) should be started, except when the risk of bleeding is very high. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab725461.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Specific recommendations from the clinical practice guidelines on elderly patients with atrial fibrillation." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:54 [ 0 => array:3 [ "identificador" => "bib0275" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stroke prevention in atrial fibrillation in older adults: existing knowledge gaps and areas for innovation: a summary of an American Federation for Aging research seminar" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. 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      "titulo" => "Prevalence of depression in type 2 diabetes mellitus"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">An 83-year-old man&#44; with arterial hypertension and diabetes&#44; experienced a hip fracture 2 months ago due to an accidental fall&#44; which was treated with a total hip prosthesis&#46; The patient was treated with 50<span class="elsevierStyleHsp" style=""></span>mg&#47;day of losartan&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day of amlodipine and 850<span class="elsevierStyleHsp" style=""></span>mg&#47;day of metformin&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">During a routine examination&#44; the attending physician detected atrial fibrillation of uncertain origin&#46; The patient was asymptomatic from a cardiology standpoint&#46; The physical examination was anodyne&#44; although arrhythmia was detected in the auscultation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Due to the recent fall&#44; the decision was made to anticoagulate the patient with acetylsalicylic acid &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; Three months later&#44; the patient was admitted to the hospital with a stroke&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The clinical problem</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Epidemiological aspects</span><p id="par0020" class="elsevierStylePara elsevierViewall">Atrial fibrillation &#40;AF&#41; is the most common type of arrhythmia in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> The Anticoagulation and Risk Factors in Atrial Fibrillation &#40;ATRIA&#41; study&#44; conducted in the United States&#44; observed that AF affects approximately 1&#37; of the general population&#44; although this percentage increases with age from 0&#46;1&#37; in participants younger than 55 years to 9&#37; in those participants aged 80 years or more&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">2</span></a> The same trend has been observed in Europe&#59; it has been estimated that the prevalence of AF is less than 1&#37; in participants aged 55&#8211;59 years and approximately 18&#37; in those who are at least 85 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> The VAL-FAAP study analyzed approximately 120&#44;000 participants treated in primary care in Spain&#46; The prevalence of AF was 6&#46;1&#37;&#44; a figure that increased with age from somewhat less than 1&#37; in participants younger than 50 years to 17&#46;6&#37; for those 80 years or older&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a> In the Observation of Atrial Fibrillation and Coronary Disease in Spain &#40;<span class="elsevierStyleItalic">Observaci&#243;n de Fibrilaci&#243;n Auricular y Enfermedad Coronaria en Espa&#241;a</span>&#44; OFRECE&#41; study that analyzed participants 40 years of age and older treated in primary care&#44; the prevalence of AF was 4&#46;4&#37; and progressively increased starting at 60 years of age&#44; reaching 17&#46;7&#37; in those older than 80 years&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> In the DARIOS study that analyzed 6 population-based studies&#44; the prevalence of AF was 1&#46;5&#37;&#44; a figure that increased with the age&#44; up to 6&#46;3&#37; in those older than 75 years&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a> Data from the ESFINGE study show that a third of patients older than 70 years hospitalized in the national departments of internal medicine have AF&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The prevalence of AF not only increases with age but also with the presence of other associated comorbidities&#44; such as ischemic heart disease and heart failure&#44; conditions that are also more prevalent in advanced ages&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">8&#44;9</span></a> Due to the progressive aging of the population&#44; both the prevalence and incidence of AF has increased markedly in recent years&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">AF increases the risk of stroke by up to 5-fold&#46; More than 15&#37; of stroke episodes are due to AF &#40;36&#37; in individuals older than 80 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">9</span></a> Additionally&#44; stroke associated with AF&#44; when compared with stroke unrelated to AF&#44; has higher morbidity and mortality and causes more sequela and hospitalizations&#44; especially in the elderly&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the elderly population&#44; the treatment objectives for patients with AF should be focused on preventing complications related to the presence of this arrhythmia&#44; especially stroke&#44; as well as on improving quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a> In this context&#44; anticoagulation plays a fundamental role&#46; However&#44; it is particularly important with the elderly population to balance the risk of both stroke and bleeding&#44; given that both are increased in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The objective of this update was to review the specific comments by the clinical practice guidelines on antithrombotic treatment in elderly patients with nonvalvular AF &#40;NVAF&#41;&#46; It is important to emphasize that the definition of the elderly patient has changed over time&#46; Although in the past elderly patients were considered those aged 65 years or older&#44; the various current clinical practice guidelines and the studies performed with direct oral anticoagulants have raised this cutoff to 75 years&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical profile of elderly patients with atrial fibrillation</span><p id="par0045" class="elsevierStylePara elsevierViewall">The management of elderly patients with AF is complex due to&#44; among other things&#44; their considerable number of comorbidities&#44; which often result in polymedication&#46; Thus&#44; it has been observed among patients with hypertension and chronic ischemic heart disease that those with AF are older and more often present diabetes&#44; left ventricular hypertrophy&#44; heart failure&#44; peripheral arterial disease&#44; renal failure and stroke&#44; when compared with those in sinus rhythm&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">9</span></a> Moreover&#44; it appears that patients with AF have an increased risk of dementia&#44; particularly those with a history of stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> In fact&#44; there are various peculiarities in the elderly that confer a condition of frailty&#46; Physical and mental abnormalities are common&#44; especially cognitive and mood disorders&#44; risk of falls&#44; malnutrition and social dependence&#44; which have a significant impact on the management of these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Advanced age is itself an independent predictor of both stroke and mortality after the stroke&#44; as well as the risk of bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">16&#8211;20</span></a> This aspect is considered in the risk scales&#46; On the CHADS<span class="elsevierStyleInf">2</span> scale&#44; an age &#8805;75 years scores 1 point&#44; reinforcing the increase in risk with increasing age&#46; For the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc scale&#44; an age between 65 and 74 years is awarded 1 point&#44; increasing to 2 for ages &#62;75 years&#46; In terms of the risk of bleeding&#44; an age &#62;65 years scores 1 point on the HAS-BLED &#40;Hypertension&#44; Abnormal Renal&#47;Liver Function&#44; Stroke&#44; Bleeding History or Predisposition&#44; Labile INR&#44; Elderly&#44; Drugs&#47;Alcohol Concomitantly&#41; scale&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">17&#8211;20</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Consequently&#44; taking into account the above described determinants&#44; it is especially important for elderly patients to not only balance the risk of stroke with that of hemorrhage but also to assess the possibility of properly taking medication&#44; the availability of a caregiver&#44; the social support&#44; etc&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">12&#44;21</span></a> In principle&#44; except when the patient has a high risk of bleeding&#44; the considerable majority of elderly patients with NVAF should undergo permanent anticoagulation&#46; Nevertheless&#44; the Birmingham Atrial Fibrillation Treatment of the Aged &#40;BAFTA&#41; study found no evidence that&#44; when compared with acetylsalicylic acid&#44; anticoagulation provided clinically relevant protection against cognitive impairment in patients after 33 months of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">22</span></a> A decision algorithm has recently been proposed for better profiling geriatric patients with NVAF who will most benefit from treatment with vitamin K antagonists&#46; The algorithm includes 6 items &#40;previous bleeding with vitamin K antagonists&#44; degree of autonomy&#44; mini mental state examination &#91;MMSE&#93; score&#44; risk of falls and comorbidity index&#41;&#46; Each variable has a score &#40;0&#44; 0&#46;5 and 1 point&#41; according to the intensity &#40;mild&#44; moderate or high&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">23</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the peculiarities of AF in this age group&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Strategies and evidence</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Anticoagulation with vitamin K antagonists for elderly patients</span><p id="par0065" class="elsevierStylePara elsevierViewall">Traditionally&#44; anticoagulation for patients with AF has been performed with vitamin K antagonists&#46; In fact&#44; it has been shown that anticoagulant therapy with vitamin K antagonists is an effective treatment for the prevention of stroke and thromboembolism when compared with antiplatelet agents&#44; including acetylsalicylic acid&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">24&#44;25</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Anticoagulant treatment with vitamin K antagonists is also beneficial for the elderly population&#46; The BAFTA study compared warfarin treatment with acetylsalicylic acid treatment &#40;75<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; with approximately 1000 participants 75 years of age or older with AF who were followed-up for a mean time of 2&#46;7 years&#46; The warfarin treatment was associated with a significant reduction &#40;52&#37;&#41; in the risk of fatal or debilitating stroke&#44; intracranial hemorrhage and clinically significant arterial embolism&#44; with no significant differences in the risk of extracranial hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">26</span></a> Subsequent studies have confirmed the benefits of anticoagulation in this population&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">27&#44;28</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Although it is certain that the risk of bleeding is increased in elderly patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">19&#44;29</span></a> permanent anticoagulation is indicated for the majority of elderly patients with AF&#46; However&#44; the reality is that a significant number of patients who have an indication for anticoagulation do not receive it&#44; precisely because of the fear of bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">9&#44;30&#8211;34</span></a> In a study performed with approximately 600 participants with NVAF&#44; only 34&#37; of the participants were treated with anticoagulation at discharge&#46; This percentage was even lower for the more elderly participants &#40;42&#37; among individuals aged 65&#8211;75 years and 29&#37; for those older than 75 years&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> In addition to bleeding&#44; the factors that promote this situation include falls&#44; which should never be an absolute contraindication for anticoagulation&#46; However&#44; given that frequent falls in elderly patients with AF are associated with higher mortality&#44; in the patient group with a lower CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score &#40;e&#46;g&#46;&#44; 0&#8211;3&#41;&#44; the decision to provide anticoagulation therapy to the patient should be made by carefully assessing the risk&#47;benefit ratio&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">35</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Vitamin K antagonists have certain limitations&#44; such as their narrow therapeutic window&#44; variable anticoagulant response&#44; interactions with food and other drugs and a slow start and end of action&#44; which require the implementation of periodic checkups and frequent dosage adjustments &#40;more common in the elderly&#41;&#46; These limitations undoubtedly contribute to the underutilization of these drugs in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Direct oral anticoagulants in elderly patients</span><p id="par0085" class="elsevierStylePara elsevierViewall">Direct oral anticoagulants &#40;dabigatran&#44; rivaroxaban&#44; apixaban and&#44; more recently&#44; edoxaban&#41; have at least a similar efficacy as warfarin in preventing stroke and systemic embolism but have a better safety profile&#44; mainly due to the lower risk of intracranial hemorrhage for patients with NVAF&#46; In addition to having predictable kinetics and a broad therapeutic window&#44; these anticoagulants can be prescribed at a fixed dosage&#44; without the need for periodic checkups&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">36</span></a> Clinical trials specifically designed to assess the safety and efficacy of these drugs in elderly populations have unfortunately not been performed&#46; However&#44; in recent years&#44; various subanalyses have been published on the safety and efficacy of direct oral anticoagulants by age&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the RE-LY study that compared dabigatran to warfarin&#44; both dabigatran dosages had a lower risk of both intracranial and extracranial bleeding in the participants younger than 75 years&#46; The patients aged 75 years or older had less frequent intracranial bleeding&#44; but the extracranial bleeding was equal or more frequent&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">37</span></a> Given that the elimination of dabigatran is performed mainly by the kidneys and that the elderly frequently have renal failure&#44; close monitoring of renal function is important for these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> Although the standard recommended dosage for dabigatran is 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; it is recommended that the dosage be reduced to 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h for patients aged 80 years or older&#46; For patients aged 75&#8211;80 years or with moderate renal failure&#44; the dosage is selected depending on the risk of stroke&#47;bleeding&#46; In the ROCKET-AF study &#40;An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation&#41; that compared warfarin to rivaroxaban&#44; the efficacy &#40;risk of stroke and systemic embolism&#41; and safety &#40;risk of major bleeding&#41; of rivaroxaban were consistent with the overall study results&#44; regardless of age&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">39</span></a> In the Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation &#40;ARISTOTLE&#41; study&#44; apixaban was more effective in reducing the risk of stroke and mortality&#44; with fewer major bleeding episodes&#44; total bleeding episodes and intracranial bleeding episodes&#44; regardless of age&#44; including with patients aged 80 years or older&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">40</span></a> In a recent meta-analyses of patients aged 75 years or older enrolled in clinical trials performed with rivaroxaban&#44; apixaban and dabigatran&#44; the direct oral anticoagulants as a whole were more effective than standard treatment in the prevention of stroke and systemic embolism&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">41</span></a> In the ENGAGE AF-TIMI 48 study&#44; both edoxaban dosages were noninferior to warfarin with respect to preventing stroke and systemic embolism but had fewer major bleeding episodes&#44; regardless of age &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">42</span></a><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows how the dosage adjustments for dabigatran&#44; rivaroxaban and apixaban should be performed for patients with NVAF&#44; depending on age&#44; renal function and weight&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">43&#8211;45</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Controversy and issues to be resolved</span><p id="par0095" class="elsevierStylePara elsevierViewall">Despite the recent proliferation of guidelines that&#44; to various degrees&#44; refer to the elderly&#44; the evidence in this population group is scarce&#44; and there are a number of unresolved issues that are frequently faced by clinicians in their daily practice&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A number of these issues are examined below&#46; The major advantage of direct oral anticoagulants is the reduction in intracranial hemorrhage&#46; In addition&#44; there are data from neuroimaging tests &#40;e&#46;g&#46;&#44; microinfarctions&#44; leukoaraiosis&#44; and microhemorrhages&#41; that are associated with an increased risk of intracranial hemorrhage&#44; particularly in cases where there is a history of ischemic stroke&#46; Given this&#44; should a brain CT scan&#47;MRI be performed for elderly patients with an indication of anticoagulation&#44; due to their greater risk of bleeding and high prevalence of the previously mentioned lesion&#63; What type of antithrombotic treatment is the treatment of choice for an elderly patient with a history of frequent falls&#63; In what way does cognitive impairment determine the indication and type of antithrombotic treatment in elderly patients with AF&#63; How often and under what circumstances should renal function be monitored in elderly patients undergoing anticoagulation&#63; Under what circumstances is the temporary or definitive withdrawal of anticoagulation recommended for the elderly&#63; How should antithrombotic treatment be managed for patients with a high risk of gastrointestinal bleeding&#63; How does polypharmacy and poorer treatment compliance influence the choice of anticoagulant treatment for the elderly&#63; How should weight and frailty affect the dosage of direct oral anticoagulants in elderly patients&#63; Are there sufficient data on their safety and efficacy to recommend direct oral anticoagulants to very elderly patients&#63; The answers to these questions will probably only be found when sufficient experience in the real world is available&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">What do the clinical practice guidelines say on this matter&#63;</span><p id="par0105" class="elsevierStylePara elsevierViewall">In recent years&#44; various clinical practice guidelines have been published on managing patients with AF&#46; Although the recommendations are generally given regardless of age&#44; a number have specific comments on elderly populations&#44; which we will review below&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In 2010&#44; the European Society of Cardiology published guidelines for the management of patients with AF&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a> These guidelines dedicate a specific paragraph to elderly populations&#46; Among other issues&#44; the guidelines state that AF is more common the older the patient and provide the clinical characteristics of this population&#46; Furthermore&#44; the guidelines emphasize that a strategy of heart rate control is preferable to rhythm control in the elderly population&#46; For the risk stratification of stroke and bleeding&#44; the guidelines propose the use of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc and HAS-BLED scales&#46; Unless contraindicated&#44; anticoagulation is recommended&#46; The benefit of antiplatelet treatment is highly limited in this population&#44; given that the risk of major bleeding episodes is very similar to that of anticoagulation&#44; while antiplatelet treatment is much less effective in terms of preventing stroke and cardiovascular events&#46; It has been suggested that an international normalized ratio &#40;INR&#41; range between 1&#46;8 and 2&#46;5 would be safer for the elderly population who undergo anticoagulation with vitamin K antagonists&#46; However&#44; the reality is that this range has not been endorsed by any clinical trial&#46; Cohort studies have suggested an increased risk of stroke with an INR range of 1&#46;5&#8211;2&#46;0&#59; therefore&#44; it is recommended that the INR not fall below 2&#46;0&#46; Only RE-LY study data have been published and the European Medicines Agency &#40;EMA&#44; <a href="http://www.ema.europa.eu/">http&#58;&#47;&#47;www&#46;ema&#46;europa&#46;eu&#47;</a>&#41; has not approved the use of vitamin K in patients with NVAF&#46; However these guidelines recommend the use of vitamin K antagonists&#44; although they make a number of general recommendations on the use of dabigatran &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">The update to these guidelines was published in 2012&#46; These guidelines continue to recommend the use of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc and Has-BLED scales and emphasize the lack of benefit from acetylsalicylic acid&#46; They also comment on the results of 3 clinical trials with direct oral anticoagulants &#40;RE-LY&#44; ROCKET-AF and ARISTOTLE&#41; and the concern regarding its applicability to more elderly populations&#46; For patients aged 80 years and older&#44; the dabigatran dosage to be used is 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The proposed guidelines by the American Heart Association and the American Stroke Association for the primary prevention of stroke emphasize the need to control arterial hypertension in the elderly &#40;mainly systolic blood pressure&#41;&#44; which&#44; along with appropriate antithrombotic treatment&#44; are essential for preventing the development of stroke in patients with AF&#46; In most elderly patients with stable ischemic heart disease and AF&#44; anticoagulant treatment is sufficient&#46; Moreover&#44; the detection of brain microhemorrhages in MRI could be useful when assessing the safety of antithrombotic treatment in an elderly patient &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">46</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The 2012 Canadian AF guidelines indicate that advanced age &#40;&#62;75<span class="elsevierStyleHsp" style=""></span>years&#41; is considered a risk factor not only for stroke but also for hemorrhage&#44; particularly intracranial&#46; The use of the CHADS<span class="elsevierStyleInf">2</span>&#44; CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc and HAS-BLED scales is recommended&#46; With regard to direct oral anticoagulants&#44; dosage reductions are recommended for patients older than 75 years&#44; especially for those older than 80 and especially with dabigatran&#46; Moreover&#44; all patients with AF undergoing treatment with anticoagulants should undergo periodic monitoring of their renal function at least once a year &#40;more frequently in cases of renal failure&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The recommendations proposed by the American College of Chest Physicians are not substantially different according to the age&#46; They do however specify that the risk of stroke increases with age&#44; as reflected in the CHADS<span class="elsevierStyleInf">2</span> risk stratification scale&#44; as well as the risk of bleeding &#40;older than 65 years on the HAS-BLED scale&#44; older than 75 years on the HEMORR<span class="elsevierStyleInf">2</span>HAGES scale&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The guidelines of the European Heart Rhythm Association&#44; which specifically cover the use of direct oral anticoagulants in patients with NVAF&#44; insist on the need for renal function monitoring&#46; That is especially relevant in elderly patients &#40;older than 75 years&#41; or those who are taking dabigatran&#46; For patients with active cancer&#44; vitamin K antagonists or heparins are preferred over direct oral anticoagulants&#44; given the lack of experience with the latter in this context and possibility of interactions with chemotherapy drugs&#46; In the event that antiplatelet therapy is considered necessary in the first year after an acute ischemic episode&#44; the use of low doses of direct oral anticoagulants is considered safer&#44; especially for patients with HAS-BLED scores &#8805;3&#46; In this context&#44; vitamin K antagonists &#40;INR objective 2&#8211;2&#46;5&#41; might be preferable&#44; especially for very elderly populations and for those with renal failure &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The guidelines of the Spanish Society of Neurology recommend anticoagulation&#44; except when contraindicated&#44; for patients with NVAF and a high risk of stroke &#40;patients older than 75 years&#41;&#46; For these patients&#44; both vitamin K antagonists and direct oral anticoagulants may be used&#46; In fact&#44; the guidelines specifically indicate that despite the hemorrhagic risk&#44; oral anticoagulants show a clear benefit in patients older than 85 years who have AF &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">50</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The guidelines of the American College of Cardiology&#44; American Heart Association and Heart Rhythm Society have been recently published&#46; These guidelines have a specific section dedicated to the elderly population that indicates that the prevalence of AF increases with age and that the presence of other comorbidities is more common&#46; Clinicians usually opt for a heart rate control strategy&#44; more so than a rhythm control strategy&#44; especially considering the possibility of the adverse effects of antiarrhythmic agents in this population&#46; The use of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc scale is recommended&#44; as well as anticoagulation&#44; for patients aged 75 years or older&#44; either with vitamin K antagonists or direct oral anticoagulants&#44; except where contraindicated&#46; Patients&#8217; renal function should be measured before starting treatment with direct oral anticoagulants&#44; as well as subsequently during monitoring at least once a year &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">51</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Similarly&#44; guidelines proposed by a subcommittee of the American Academy of Neurology have been recently published&#46; These guidelines recognize the benefit of anticoagulation in elderly patients &#40;older than 75 years&#41;&#46; The main recommendation of these guidelines is that&#44; except where there is recent spontaneous bleeding or intracranial hemorrhage&#44; anticoagulation should be proposed for all elderly patients with NVAF&#44; including patients with mild dementia or occasional falls&#46; However&#44; the benefit of anticoagulation in patients with moderate to severe dementia or with frequent falls is uncertain &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">52</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The recent NICE guidelines recommend&#44; on one hand&#44; a heart rate control strategy and&#44; on the other&#44; anticoagulation for those participants with NVAF and a CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score &#8805;2&#46; Apixaban&#44; dabigatran&#44; rivaroxaban and vitamin K antagonists may be used&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">53</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">In summary&#44; the various clinical practice guidelines as a whole recognize that elderly patients with AF are complex patients with numerous comorbidities and who are frequently polymedicated&#46; All elderly patients with AF should &#40;unless contraindicated&#41; undergo permanent anticoagulant treatment&#44; although it is important to assess the risk of bleeding&#46; In terms of the type of oral anticoagulant to use in the elderly population&#44; both vitamin K antagonists and direct oral anticoagulants may be used in these patients&#46; If the latter are used&#44; it is important that renal function be monitored during follow-up&#44; especially when the patient has known renal failure or is taking dabigatran&#46; Unfortunately and despite the fact that the recommendations of the clinical practice guidelines appear clear&#44; a study performed with patients with NVAF in Spain found that 42&#37; of patients did not follow the recommendations of the European Society of Cardiology&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">54</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">How should our patient have been evaluated and treated&#63;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Before the stroke&#44; this patient already presented a very high risk of thromboembolic complications &#40;CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc&#58; 4&#59; 2 points for age&#59; 1 point for hypertension and 1 point for diabetes&#41;&#46; The patient should have therefore undergone anticoagulation&#46; The two factors that had the greatest weight for not starting anticoagulation were the history of casual falls and the patient&#39;s age&#44; despite the high thromboembolic risk he had&#44; as subsequently happened&#46; The patient underwent anticoagulation after the stroke&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In conclusion&#44; the management of NVAF in the elderly is complicated&#44; and&#44; due to the increased risk of thromboembolic complications and hemorrhage&#44; the decision to administer anticoagulation therapy should be individualized&#46; There are still unresolved questions and lack of evidence in this population&#46; Data from observational studies in our standard practice are needed and are important for the decision-making process&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0175" class="elsevierStylePara elsevierViewall">Editorial assistance was provided by Content Ed Net and sponsored by Bayer&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">Dr&#46; Carmen Su&#225;rez has received has received honoraria for lectures and advising from BMS&#44; Pfizer&#44; Boheringher&#44; Bayer and Daichii Sankyo&#46; Dr&#46; Francesc Formiga has received honoraria for lectures and advising from BMS&#44; Pfizer&#44; Boheringher&#44; Bayer and Daichii Sankyo Dr&#46; A pose Reino declares having received honoraria for lectures and advising from BMS&#44; Pfizer&#44; Boheringher and Bayer&#46; The remaining authors declare having no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Clinical profile of elderly patients with atrial fibrillation"
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          "titulo" => "Strategies and evidence"
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              "titulo" => "Anticoagulation with vitamin K antagonists for elderly patients"
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              "titulo" => "Direct oral anticoagulants in elderly patients"
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          "titulo" => "Controversy and issues to be resolved"
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          "titulo" => "What do the clinical practice guidelines say on this matter&#63;"
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    "fechaRecibido" => "2014-10-10"
    "fechaAceptado" => "2014-11-30"
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          "clase" => "keyword"
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          "palabras" => array:8 [
            0 => "Elderly"
            1 => "Nonvalvular atrial fibrillation"
            2 => "Guidelines"
            3 => "Vitamin K antagonists"
            4 => "Dabigatran"
            5 => "Rivaroxaban"
            6 => "Apixaban"
            7 => "Edoxaban"
          ]
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          "palabras" => array:8 [
            0 => "Anciano"
            1 => "Fibrilaci&#243;n auricular no valvular"
            2 => "Gu&#237;as"
            3 => "Antagonistas de la vitamina K"
            4 => "Dabigatran"
            5 => "Rivaroxaban"
            6 => "Apixaban"
            7 => "Edoxaban"
          ]
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Atrial fibrillation &#40;AF&#41; in the elderly is a complex condition due to the high number of frequently associated comorbidities&#44; such as cardiovascular and kidney disease&#44; cognitive disorders&#44; falls and polypharmacy&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Except when contraindicated&#44; anticoagulation is necessary for preventing thromboembolic events in this population&#46; Both vitamin K antagonists and direct oral anticoagulants &#40;dabigatran&#44; rivaroxaban and apixaban&#41; are indicated in this context&#46; Renal function should be closely monitored for this age group when these drugs are used&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In recent years&#44; various clinical practice guidelines have been published on patients with AF&#46; The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients&#46; In this update&#44; we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La fibrilaci&#243;n auricular &#40;FA&#41; en el anciano es una entidad compleja debido al elevado n&#250;mero de comorbilidades frecuentemente asociadas&#44; como las enfermedades cardiovasculares y la enfermedad renal&#44; los trastornos cognitivos&#44; las ca&#237;das o la polimedicaci&#243;n&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Excepto cuanto est&#233; contraindicada&#44; la anticoagulaci&#243;n es necesaria para la prevenci&#243;n de los eventos tromboemb&#243;licos en esta poblaci&#243;n&#46; Tanto los antagonistas de la vitamina K como los anticoagulantes orales de acci&#243;n directa &#40;dabigatran&#44; rivaroxaban y apixaban&#41; est&#225;n indicados en este contexto&#46; En este grupo de edad la funci&#243;n renal debe ser estrechamente vigilada cuando se utilizan estos &#250;ltimos&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En los &#250;ltimos a&#241;os se han publicado diferentes gu&#237;as de pr&#225;ctica cl&#237;nica sobre el paciente con FA&#46; La mayor&#237;a de estas gu&#237;as realizan recomendaciones espec&#237;ficas sobre las caracter&#237;sticas cl&#237;nicas y el tratamiento en los pacientes ancianos&#46; En esta actualizaci&#243;n se revisan los comentarios espec&#237;ficos sobre las recomendaciones referentes al tratamiento antitromb&#243;tico en los pacientes ancianos con FA no valvular&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Su&#225;rez Fern&#225;ndez C&#44; Camafort M&#44; Cepeda Rodrigo JM&#44; D&#237;ez-Manglano J&#44; Formiga F&#44; Pose Reino A&#44; et al&#46; Tratamiento antitromb&#243;tico en el paciente anciano con fibrilaci&#243;n auricular&#46; Rev Clin Esp&#46; 2015&#59;215&#58;171&#8211;181&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>&#58; AF&#44; atrial fibrillation&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Adapted from&#58; Lubitz et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> Go et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">2</span></a> Heeringa et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> Barrios et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a> G&#243;mez-Doblas et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> Baena-D&#237;ez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a> L&#243;pez Soto et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">7</span></a> Rodr&#237;guez-Ma&#241;ero et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> Barrios et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">9</span></a> Freedman et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">10</span></a> M&#233;rida-Rodrigo et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a> Hanon et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a> R&#248;nning et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">16</span></a> Camm et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a> Camm et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a> Pisters et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">19</span></a> Lip et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">20</span></a> Mant et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">26</span></a> Lip and Lane&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">27</span></a> Siu and Tse&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">28</span></a> Formiga et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">30</span></a> Gage et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> Gao et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">32</span></a> Darnell et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">33</span></a> and Fuenzalida et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">34</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">The prevalence and incidence of AF increase with age&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Stroke associated with AF&#44; when compared with stroke unrelated to AF&#44; has increased mortality and morbidity and more sequela&#44; especially in the elderly&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Elderly patients with AF have a higher number of hospitalizations&#44; increased mortality and generate a greater degree of dependence when compared with younger patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Elderly patients have a considerable number of comorbidities&#44; which frequently results in polymedication&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">They also have other physical and mental disorders&#44; especially cognitive and mood disorders&#44; risk of falls&#44; malnutrition and social dependence&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">They are frequently underdiagnosed&#44; given that AF often progresses in the elderly asymptomatically or with few symptoms&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Advanced age is an independent predictor of stroke and mortality after stroke&#44; as well as a risk of bleeding&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Except where contraindicated&#44; elderly patients with AF should undergo anticoagulation&#46; However&#44; many are not due to the fear of bleeding&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Peculiarities of atrial fibrillation in the elderly patient&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; NVAF&#44; nonvalvular atrial fibrillation&#59; CrCl&#44; creatinine clearance&#59; ITT&#44; intention to treat&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Adapted from Eikelboom et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">37</span></a> Halperin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">39</span></a> Halvorsen et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">40</span></a> and Giugliano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">42</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Population&#47;comparator groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">RE-LY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#44;113 patients &#40;mean age&#44; 71&#46;5 years&#59; 40&#46;1&#37; &#8805;75<span class="elsevierStyleHsp" style=""></span>years&#59; mean CHADS<span class="elsevierStyleInf">2</span> score&#44; 2&#46;1&#41; with NVAF were randomized to dabigatran 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; dabigatran 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h or warfarin&#46; Mean follow-up&#44; 2&#46;0 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">When compared with warfarin&#44; both dabigatran dosages &#40;110<span class="elsevierStyleHsp" style=""></span>mg and 150<span class="elsevierStyleHsp" style=""></span>mg twice daily&#41; presented a lower risk of intracranial and extracranial bleeding in participants younger than 75 years&#46; For participants 75 years or older&#44; intracranial bleeding was less frequent but extracranial was the same or more frequent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ROCKET-AF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44;264 patients with NVAF &#40;mean age&#44; 73 years&#59; 44&#37; &#8805;75 years&#59; mean CHADS<span class="elsevierStyleInf">2</span> score&#44; 3&#46;4&#41; were randomized to rivaroxaban &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#59; 15<span class="elsevierStyleHsp" style=""></span>mg if CrCl &#60;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#41; in comparison with warfarin&#46; Mean follow-up of 707 days in the ITT analysis&#59; 590 days in the per-protocol analysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The elderly patients had a greater risk of stroke and major bleeding episodes when compared with the younger patients&#46;The efficacy &#40;risk of stroke and systemic embolism&#41; and safety &#40;risk of major bleeding episodes&#41; of rivaroxaban when compared with warfarin were consistent with the overall results of the study&#44; regardless of age&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#44;201 patients &#40;mean age&#44; 70 years&#59; 31&#37; &#8805;75 years&#59; 13&#37; &#8805;80 years&#59; mean CHADS<span class="elsevierStyleInf">2</span> score&#44; 2&#46;1&#41; with NVAF were randomized to apixaban 5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h &#40;or 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h in case &#8805;2 of the following criteria were met&#58; age &#8805;80 years&#44; weight &#8804;60<span class="elsevierStyleHsp" style=""></span>kg&#44; or creatinine level &#8805;133<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#41; or warfarin&#46; Mean follow-up&#44; 1&#46;8 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Apixaban was more effective in reducing the risk of stroke and mortality&#44; with fewer major bleeding episodes&#44; total bleeding episodes and intracranial bleeding episodes&#44; regardless of age&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ENGAGE AF-TIMI 48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#44;105 patients &#40;mean age&#44; 72 years&#59; 40&#46;1&#37; &#8805;75 years&#59; mean CHADS<span class="elsevierStyleInf">2</span> score&#44; 2&#46;8&#41; with NVAF were randomized to edoxaban 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; edoxaban 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day or warfarin&#46; Mean follow-up&#44; 2&#46;8 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Both edoxaban dosages &#40;30 and 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; were noninferior to warfarin with respect to preventing stroke and systemic embolism but had fewer major bleeding episodes&#44; regardless of age&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Results of the RE-LY&#44; ROCKET-AF&#44; ARISTOTLE and ENGAGE AF-TIMI 48 studies by age&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; CrCl&#44; creatinine clearance&#59; NVAF&#44; nonvalvular atrial fibrillation&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Adapted from&#58; European Medicines Agency &#40;EMA&#41;&#44; Pradaxa<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">43</span></a>&#59; European Medicines Agency &#40;EMA&#41;&#44; Xarelto<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a>&#59; and European Medicines Agency &#40;EMA&#41;&#44; Eliquis<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">45</span></a>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosage adjustment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Dabigatran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">Based on age</span>&#58;<span class="elsevierStyleHsp" style=""></span>&#8226; 75 years&#58; 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#8226; 75&#8211;80 years&#58; 150 or 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; depending on thrombotic&#47;hemorrhagic risk<span class="elsevierStyleHsp" style=""></span>&#8226; &#8805;80 years&#58; 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#8226; <span class="elsevierStyleItalic">Based on renal function&#58;</span>If CrCl &#8805;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; dosage adjustment not necessary&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl is 30&#8211;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; assess 150<span class="elsevierStyleHsp" style=""></span>mg or 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; depending on thrombotic&#47;hemorrhagic risk&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; contraindicated&#8226; <span class="elsevierStyleItalic">Concomitant use of verapamil&#58; 110</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;12</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h</span>&#8226; <span class="elsevierStyleItalic">Based on weight&#58; A dosage adjustment is not necessary&#44; although close follow-up is recommended for patients weighing &#60;50</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kg</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rivaroxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">Based on age&#58; No dosage adjustment required</span>&#8226; <span class="elsevierStyleItalic">Based on renal function&#58;</span><span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl &#8805;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; recommended dosage is 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl is 15&#8211;49<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; recommended dosage is 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl &#60;15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; not recommended&#46;&#8226; <span class="elsevierStyleItalic">Based on weight&#58; No dosage adjustment required</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Apixaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">In general&#44; the recommended dosage is 5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;12</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h&#46; The dosage should be reduced to 2&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;12</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h for NVAF and &#8805;2 of the following criteria&#58; &#8805;80 years&#44; &#8804;60</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kg or serum creatinine level &#8805;1&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;dL&#46;</span>&#8226; <span class="elsevierStyleItalic">Based on age&#58; No dosage adjustment required&#44; except for age &#8805;80 years&#44; weight &#8804;60</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kg or creatinine level &#8805;1&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;dL&#46;</span>&#8226; <span class="elsevierStyleItalic">Based on renal function&#58;</span><span class="elsevierStyleHsp" style=""></span>&#8226; Dosage adjustments are not required for patients with mild to moderate renal failure&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If creatinine level is &#8805;1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#58; recommended dosage is 5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; except for patients &#8805;80 years or &#8804;60<span class="elsevierStyleHsp" style=""></span>kg for whom the dosage should be reduced to 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl is 15&#8211;29<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#58; recommended dosage is 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46;<span class="elsevierStyleHsp" style=""></span>&#8226; If CrCl is &#60;15<span class="elsevierStyleHsp" style=""></span>mL&#47;min or on dialysis&#58; not recommended&#46;&#8226; <span class="elsevierStyleItalic">Based on weight&#58; No dosage adjustment required&#44; except for age &#8805;80 years&#44; weight &#8804;60</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kg or creatinine level &#8805;1&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;dL&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Dosage adjustment of dabigatran&#44; rivaroxaban and apixaban for patients with nonvalvular atrial fibrillation&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; ESC&#44; European Society of Cardiology&#59; NICE&#44; National Institute for Health and Care Excellence&#59; SEN&#44; Spanish Society of Neurology&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Adapted from Camm et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a> Camm et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a> EMA Pradaxa<span class="elsevierStyleSup">&#174;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">43</span></a> EMA Xarelto<span class="elsevierStyleSup">&#174;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> EMA Eliquis<span class="elsevierStyleSup">&#174;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">45</span></a> Goldstein et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">46</span></a> Skanes et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a> You et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a> Heidbuchel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a> and Fuentes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">50</span></a></p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Guidelines &#40;year of publication&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ESC &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Specific section dedicated to the elderly population&#46;Compared with younger patients&#44; the elderly&#58;Are frailer and have more comorbidities&#46;Permanent AF is more common than paroxysmal&#47;persistent AF&#46;Atypical symptoms are more common&#46;They have a greater likelihood of presenting adverse effects from the drugs&#46;They are frequently underdiagnosed&#46;In general&#44; a heart rate control strategy is preferred over a rhythm control strategy&#46;Given that patients older than 75 years with AF have a &#62;4&#37; annual risk of presenting thromboembolic complications&#44; anticoagulation is indicated unless the risk of bleeding is very high &#40;the benefit of antiplatelet therapy is very limited in this population&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">American Heart Association&#47;American Stroke Association &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">To prevent stroke in the elderly&#44; it is essential to control blood pressure &#40;mainly systolic&#41; and have appropriate antithrombotic treatment&#46;The effects of combining antiplatelet with anticoagulant treatment in this population have not been clearly established&#46;In most elderly patients with stable ischemic heart disease and AF&#44; anticoagulant treatment is sufficient&#46;The detection of brain microhemorrhages in MRI could be useful when assessing the safety of antithrombotic treatment in an elderly patient&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ESC &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The guidelines continue to recommend the use of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc and HAS-BLED scales for the risk stratification of stroke and bleeding&#44; respectively&#46;The guidelines emphasize the scarce benefit of aspirin for these patients&#44; with a high risk of bleeding&#44; and that its use should be limited to those patients who reject any type of anticoagulation&#46;There is concern on how to adapt the results of clinical trials with direct oral anticoagulants to the more elderly population&#44; who have numerous comorbidities and are frequently polymedicated&#44; as well as the fact that individuals with severe renal failure were excluded from these studies&#46; This is particularly important with dabigatran&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Canadian Guidelines &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The guidelines recommend the use of the CHADS<span class="elsevierStyleInf">2</span> and CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc scales for the risk stratification of stroke and the HAS-BLED scale for assessing the risk of bleeding&#46;With regard to direct oral anticoagulants&#44; dosage reductions are recommended for patients older than 75 years&#44; especially for those older than 80 and especially with dabigatran&#46;All patients with AF undergoing treatment with anticoagulants should undergo periodic monitoring of their renal function at least once a year&#46; Patients with a glomerular filtration rate of 30&#8211;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min need a closer monitoring of their renal function and might require anticoagulant dosage reductions in certain conditions&#46; This is especially important for patients older than 75 years&#44; in whom the risk of bleeding increases significantly&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">American College of Chest Physicians &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There are no substantial differences by age&#46;The guidelines specify that the risk of stroke and bleeding increases with age&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">European Heart Rhythm Association &#40;2013&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Specific guidelines on direct oral anticoagulants for patients with NVAF&#46;The guidelines insist on the need to monitor renal function &#40;annually&#44; every 6 months and every 3 months for creatinine clearance levels &#8805;60&#44; 30&#8211;60 and &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#44; respectively&#41;&#46; This is especially relevant in elderly patients &#40;older than 75 years&#41; or those who are taking dabigatran&#46;For patients with concomitant active cancer who need anticoagulation&#44; vitamin K antagonists or heparins are preferred over direct oral anticoagulants&#46;In the event that antiplatelet therapy is considered necessary in the first year after an acute ischemic episode&#44; the use of low doses of direct oral anticoagulants is considered safer&#44; especially for patients with HAS-BLED scores &#8805;3&#46; In this context&#44; vitamin K antagonists &#40;INR objective 2&#8211;2&#46;5&#41; might be preferable&#44; especially for very elderly populations and for those with renal failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SEN &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The guidelines recommend anticoagulation for patients with NVAF and a high risk of stroke &#40;CHADS<span class="elsevierStyleInf">2</span> score &#8805;2 or CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score &#8805;1&#41;&#46; Therefore&#44; all patients older than 75 years should undergo anticoagulation&#44; except where contraindicated&#46;Vitamin K antagonists and direct oral anticoagulants may be used&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">American College of Cardiology&#47;American Heart Association&#47;Heart Rhythm Society &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Specific section dedicated to the elderly population&#46;Elderly patients have a greater possibility of presenting other comorbidities&#44; which can influence the approach&#46;Given that AF symptoms in these patients are usually scarce&#44; a heart rate control strategy is usually selected&#46;The guidelines recommend the use of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc scale for the risk stratification of stroke in patients with NVAF&#44; recommending anticoagulation &#40;either with vitamin K antagonists or direct oral anticoagulants&#41; for patients with a CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score &#8805;2&#46;Patients&#8217; renal function should be measured before starting treatment with direct oral anticoagulants&#44; as well as subsequently at least once a year&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">American Academy of Neurology &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">These guidelines recognize the benefit of anticoagulation in elderly patients &#40;older than 75 years&#41;&#46; However&#44; many physicians do not use them because they believe that there is a very high risk of bleeding&#46;Except where there is recent spontaneous bleeding or intracranial hemorrhage&#44; anticoagulation should be proposed for all elderly patients with NVAF&#44; including patients with mild dementia or occasional falls&#46;The benefit of anticoagulation in patients with moderate to severe dementia or with frequent falls is uncertain&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">NICE &#40;2014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In patients aged 75 years or older&#44; the prevalence of AF is high &#40;almost 15&#37;&#41;&#46;A heart rate control strategy is recommended over a rhythm control strategy&#46;The use of anticoagulation is recommended for patients with a CHA2DS2-VASc score &#8805;2&#46;For patients aged 75 years or older&#44; anticoagulation &#40;with apixaban&#44; dabigatran&#44; rivaroxaban or the vitamin K antagonists&#41; should be started&#44; except when the risk of bleeding is very high&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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