Review
Low-molecular-weight heparins in patients with atrial fibrillation
Heparinas de bajo peso molecular en pacientes con fibrilación auricular
J.M. Calvo
Servicio de Medicina Interna, Hospital Ciudad de Coria, Coria, Cáceres, Spain
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Calvo" "autores" => array:1 [ 0 => array:3 [ "nombre" => "J.M." "apellidos" => "Calvo" "email" => array:1 [ 0 => "Romerojm.calvo@orangemail.es" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Ciudad de Coria, Coria, Cáceres, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Heparinas de bajo peso molecular en pacientes con fibrilación auricular" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation (AF) is estimated to cause approximately 20% of all ischemic strokes.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Additionally, the risk of early recurrence of an ischemic stroke is greater in patients with AF.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> These data give an idea of the importance of proper prevention of embolic events in patients with AF.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this article, we review the evidence available on low-molecular-weight heparins (LMWHs) in 3 clinical situations: rapid onset of anticoagulation, bridging therapy (replacing long-term oral anticoagulant therapy related to an invasive procedure) and transesophageal echocardiography-guided cardioversion.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We conducted a literature search in the PubMed database to March 2016 with the keywords “low molecular weight heparin”, “atrial fibrillation” and “stroke”. We completed the search in the Cochrane Library database with the same keywords. We manually reviewed the literature references of the selected articles to identify other relevant articles.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Rapid start of anticoagulation</span><p id="par0020" class="elsevierStylePara elsevierViewall">LMWHs are employed relatively frequently in clinical practice to achieve rapid anticoagulation to prevent embolic events in patients diagnosed with AF. A clinical trial conducted on patients with recent-onset AF and a CHADS2 score ≤2, who were treated in an emergency department, compared subcutaneous tinzaparin at a dosage of 175<span class="elsevierStyleHsp" style=""></span>U/kg of body weight every 24<span class="elsevierStyleHsp" style=""></span>h in 46 patients with intravenous unfractionated heparin (UFH) in 50 patients.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> None of the participants treated with tinzaparin presented an ischemic stroke or transient ischemic attack in the first 48<span class="elsevierStyleHsp" style=""></span>h compared with 5 (10%) of those treated with UFH (all of whom had a subtherapeutic activated partial thromboplastin time) (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.04).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> There were no episodes of major hemorrhage in either of the 2 groups.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> In a retrospective observational study on hospitalized patients with chronic or recent-onset AF, none of the 78 patients treated with therapeutic dosages of enoxaparin (1<span class="elsevierStyleHsp" style=""></span>mg/kg of body weight every 12<span class="elsevierStyleHsp" style=""></span>h or 1.5<span class="elsevierStyleHsp" style=""></span>mg/kg every 24<span class="elsevierStyleHsp" style=""></span>h subcutaneously) experienced a stroke during treatment, compared with 5 (3.7%) of the 135 patients treated with lower dosages of enoxaparin. There were no cases of intracranial or fatal hemorrhage.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> The evidence on the safety and efficacy of LMWHs for achieving a rapid start to anticoagulation in patients with AF, in order to prevent embolic events, is scarce and definitive conclusions cannot be extracted.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The Heparin in Acute Embolic Stroke Trial (HAEST) study was a randomized, double-blind clinical trial that included 449 patients with acute ischemic stroke and FA.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> The study compared dalteparin (100<span class="elsevierStyleHsp" style=""></span>U/kg every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously) with acetylsalicylic acid (160<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h orally), both of which were started within 30<span class="elsevierStyleHsp" style=""></span>h of the stroke.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> There were no significant differences in the recurrence of ischemic stroke (8.5% vs. 7.5%), onset of symptomatic cerebral hemorrhage in the first 14 days (2.7% vs. 1.8%) or functional result or mortality at 14 days and at 3 months.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> The analysis of the various subgroups found no superiority for the dalteparin treatment in any of the groups.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> The analysis of the patient subgroup with presumably cardioembolic ischemic stroke of the Tinzaparin in Acute Ischemic Stroke (TAIST) study compared tinzaparin at a dosage of 175 or 100<span class="elsevierStyleHsp" style=""></span>U/kg every 24<span class="elsevierStyleHsp" style=""></span>h subcutaneously (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>256) with acetylsalicylic acid at a dosage of 300<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h orally (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>112), both of which were started within 48<span class="elsevierStyleHsp" style=""></span>h of the stroke.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> There were no differences in the recurrence of stroke in the first 10 days (1.6% vs. 1.8%), but there were more symptomatic cerebral hemorrhages in the group treated with tinzaparin (2.7% vs. 0%).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> The results of these 2 clinical trials of patients with presumably cardioembolic acute ischemic stroke show that LMWHs at therapeutic dosages within 30–48<span class="elsevierStyleHsp" style=""></span>h of the stroke do not reduce the risk of recurrence and can increase the risk of symptomatic cerebral hemorrhage when compared with acetylsalicylic acid.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">2,5</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Bridging therapy</span><p id="par0030" class="elsevierStylePara elsevierViewall">Bridging therapy consists of substituting long-term oral anticoagulant therapy in patients who will undergo an invasive procedure or surgery. The Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery (BRIDGE) study was a randomized, double-blind clinical trial that compared bridging therapy with dalteparin against placebo. The study included 1884 patients who underwent anticoagulation for AF.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> The mean CHADS2 score was 2.3 and only 1.5% of the patients had mitral stenosis. The study excluded, among others, patients with mechanical heart valve prostheses (MHVP) or a creatinine clearance <30<span class="elsevierStyleHsp" style=""></span>mL/min. Warfarin was discontinued 5 days before the procedure and restarted in the afternoon or the day after the procedure. Dalteparin was administered at a dosage of 100<span class="elsevierStyleHsp" style=""></span>U/kg every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously from 3 days to 24<span class="elsevierStyleHsp" style=""></span>h before the procedure and subsequently for 5–10 days. There were no significant differences in the rate of arterial thromboembolism at 30 days (0.3% vs. 0.4%), but there were more major hemorrhages in patients treated with dalteparin (3.2% vs. 1.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.005).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In an prospective observational registry of 2280 patients with AF and a mean CHADS2 score of 2.4, in which oral anticoagulation was discontinued due to an invasive procedure, there were no significant differences in the onset of stroke or systemic embolism at 30 days between the patients who underwent bridging therapy (in 74% of the cases with LMWHs) and those who did not undergo the therapy (0.6% vs. 0.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.3).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> The rate of major hemorrhages was greater among those who were treated with bridging therapy (3.6% vs. 1.2%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0007).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Only a minority of patients had moderate-severe mitral stenosis or a MHVP.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Another prospective series of 176 patients with AF and a mean CHADS2 score of 1.9 undergoing long-term warfarin therapy assessed a strategy consisting of administering enoxaparin (1.5<span class="elsevierStyleHsp" style=""></span>mg/kg every 24<span class="elsevierStyleHsp" style=""></span>h subcutaneously) as bridging therapy.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> There were 4 episodes (2.3%) of cardiac embolism.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another prospective registry assessed a strategy consisting of the discontinuation of the vitamin K antagonist 4–6 days before the procedure. When the international normalized ratio (INR) was <2, enoxaparin was started at a dosage of 1<span class="elsevierStyleHsp" style=""></span>mg/kg every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously in patients with normal renal function and a moderate-high risk of embolism (e.g., CHADS2 score of 3–6) or at 1<span class="elsevierStyleHsp" style=""></span>mg/kg every 24<span class="elsevierStyleHsp" style=""></span>h subcutaneously in the patients with a creatinine clearance <50<span class="elsevierStyleHsp" style=""></span>mL/min or a low risk of embolism (e.g., CHADS2 score of 0–2). The last dose of enoxaparin was administered at least 24<span class="elsevierStyleHsp" style=""></span>h before the procedure. The enoxaparin and vitamin K antagonist were restarted in the afternoon of the day of the procedure in cases of low hemorrhagic risk, after 48<span class="elsevierStyleHsp" style=""></span>h in cases of high hemorrhagic risk and after 72<span class="elsevierStyleHsp" style=""></span>h in cases of very high hemorrhagic risk.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> The study assessed 703 patients with AF with a mean age of 76 years, 358 of whom (50.9%) had a high-moderate risk of embolism; 33 (4.7%) patients underwent major surgery.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> There were no embolic events, but there were 3 cases of major hemorrhage (0.4%) in the 30 days after the procedure.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A meta-analysis of 9 studies (8 observational studies and 1 randomized trial) with a total of 1042 patients with MHVP, with or without AF, concluded that the use of LMWHs at weight-adjusted therapeutic dosages, in various conditions (bridging therapy, pregnancy or MHVP implantation) was not associated with an increased risk of embolic events or major hemorrhage, compared with UFH or vitamin K antagonists.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The BRIDGE study and a large observational prospective registry have provided evidence against bridging therapy with LMWHs in patients with low-risk AF (e.g., CHADS2 score of 0–2), because it does not reduce the risk of embolism and increases the risk of major hemorrhage.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7,8</span></a> Nevertheless, the rate of embolism is not so low in all studies on patients with low-risk AF, even when using a bridging therapy with LMWHs when discontinuing oral anticoagulation for an invasive procedure.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> The use of LMWHs might be reasonable at therapeutic dosages as a bridging therapy for patients with AF and a high risk of embolism (e.g., mitral stenosis or CHADS2 score of 3–6) or with MHVP, although there is little available evidence.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10,11</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Cardioversion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Some form of anticoagulation is indicated to prevent embolic events in patients with AF who undergo cardioversion. The Anticoagulation in Cardioversion using Enoxaparin (ACE) study included a total of 496 patients with AF who underwent electrical cardioversion (transesophageal echocardiography-guided in 431 patients).<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> The study compared enoxaparin at a dosage of 1<span class="elsevierStyleHsp" style=""></span>mg/kg every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously for 3–8 days followed by 60<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h (40<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h in patients weighing less than 65<span class="elsevierStyleHsp" style=""></span>kg) versus intravenous UFH for at least 3 days followed by a vitamin K antagonist.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> The anticoagulant therapy was maintained for a mean period of 28 days in the patients who underwent immediate cardioversion and 49 days in those who underwent deferred cardioversion.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> In the intent-to-treat analysis, the strategy with enoxaparin was not inferior at preventing embolic events (0.8% vs. 1.6%) or in the onset of major hemorrhage (0.8% vs. 2.4%).<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> Another randomized clinical trial on 155 patients with AF who underwent transesophageal echocardiography-guided cardioversion compared enoxaparin (1<span class="elsevierStyleHsp" style=""></span>mg/kg every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously) with intravenous UFH for the first 4 days, followed by warfarin in both groups.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> There were no recorded events in either of the 2 groups in the 35 days after the start of treatment.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In a randomized clinical trial of 172 patients with AF who underwent early, pharmaceutical or electrical transesophageal echocardiography-guided cardioversion, there were no embolic events in the patients previously treated with dalteparin at a dosage of 5000<span class="elsevierStyleHsp" style=""></span>U every 12<span class="elsevierStyleHsp" style=""></span>h subcutaneously or with intravenous UFH, both of which were followed by warfarin for 4 weeks.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> In a series of 242 patients with AF who underwent electrical transesophageal echocardiography-guided cardioversion (162 patients with immediate cardioversion), there were no embolic events using dalteparin at a dosage of 200<span class="elsevierStyleHsp" style=""></span>U/kg every 24<span class="elsevierStyleHsp" style=""></span>h subcutaneously (maximum 18,000<span class="elsevierStyleHsp" style=""></span>U every 24<span class="elsevierStyleHsp" style=""></span>h) until an INR in the therapeutic range was reached with warfarin.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The available evidence confirms the safety and efficacy of LMWHs in preventing embolic events in patients with AF who undergo transesophageal echocardiography-guided cardioversion.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">12–15</span></a> Even enoxaparin at the dosages used in the ACE study could be an alternative to oral anticoagulants during the weeks following the cardioversion.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="par0070" class="elsevierStylePara elsevierViewall">The available evidence on the utility of LMWHs in the rapid start of anticoagulation in patients who are diagnosed with AF is scarce but suggests that they might be effective and safe.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">3,4</span></a> It seems reasonable to avoid using LMWHs at therapeutic dosages in the first 48<span class="elsevierStyleHsp" style=""></span>h of a presumably cardioembolic ischemic stroke (associated with FA).<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">2,5</span></a> That recommendation is consistent with the American Heart Association/American Stroke Association recommendation to avoid anticoagulating in the acute phase of ischemic stroke, including presumably cardioembolic stroke.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a> Bridging therapy with LMWHs in patients with AF should not be indicated for patients with a low risk of embolism.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7,8</span></a> We should probably employ LMWHs at therapeutic dosages as bridging therapy for patients with AF and a high risk of embolism or with MHVP.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10,11</span></a> LMWHs are effective and safe in preventing embolic events in patients with AF who undergo transesophageal echocardiography-guided cardioversion.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">12–15</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The author declares that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres821241" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec818232" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres821242" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec818233" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Rapid start of anticoagulation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Bridging therapy" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Cardioversion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-04-29" "fechaAceptado" => "2016-09-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec818232" "palabras" => array:3 [ 0 => "Low-molecular-weight heparin" 1 => "Atrial fibrillation" 2 => "Stroke" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec818233" "palabras" => array:3 [ 0 => "Heparina de bajo peso molecular" 1 => "Fibrilación auricular" 2 => "Ictus" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In clinical practice, low-molecular-weight heparins are used relatively frequently in patients with atrial fibrillation to prevent embolic events. In this article, it is revised the available evidence in the following clinical situations: rapid onset of anticoagulation, bridging therapy (replacing long-term oral anticoagulant therapy around an invasive procedure) and transesophageal echocardiography-guided cardioversion.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En la práctica clínica, las heparinas de bajo peso molecular se utilizan con relativa frecuencia en pacientes con fibrilación auricular con el objetivo de prevenir eventos embólicos. En este artículo se revisa la evidencia disponible en las siguientes situaciones clínicas: inicio rápido de anticoagulación, tratamiento «puente» (en sustitución del tratamiento anticoagulante oral crónico en relación con un procedimiento invasivo) y cardioversión guiada por ecocardiograma transesofágico.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Calvo J. Heparinas de bajo peso molecular en pacientes con fibrilación auricular. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 March | 7 | 4 | 11 |
| 2018 January | 0 | 1 | 1 |
| 2017 April | 1 | 1 | 2 |
| 2016 December | 0 | 1 | 1 |
