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Vol. 222. Issue 4.
Pages 195-204 (April 2022)
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Vol. 222. Issue 4.
Pages 195-204 (April 2022)
Original article
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Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain
Características clínicas, manejo y riesgo de complicaciones a un año en pacientes con insuficiencia cardíaca con y sin diabetes tipo 2 en España
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C. Escobara,
Corresponding author
, L. Varelab, B. Palaciosb, M. Capelb, A. Sicras-Mainarc, A. Sicras-Navarroc, A. Hormigod, R. Alcázare, N. Manitof, M. Botanag
a Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain
b Departamento médico, AstraZeneca Spain
c Investigación sobre economía y resultados de la salud, Atrys Health, Barcelona, Spain
d Centro de Salud de Atención Primaria Puerta Blanca, Málaga, Spain
e Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, Spain
f Unidad de Insuficiencia Cardíaca Avanzada y Trasplante Cardíaco, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
g Servicio de Endocrinología, Hospital Universitario Lucus Augusti, Lugo, Spain
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Tables (4)
Table 1. Baseline clinical characteristics of the heart failure population at index date 1st January 2019 according to the presence of type 2 diabetes.
Table 2. Event rates after one year of follow-up.
Table 3. Event rates after one year of follow-up by age groups and by gender.
Table 4. Hospitalization outcomes after one year of follow-up.
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Abstract
Objective

This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline.

Methods

This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged ≥ 18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed.

Results

We identified 21,851 patients with HF (age 78.0 ± 11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9 ± 72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population.

Conclusions

In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF.

Keywords:
DAPA-HF
Death
Heart failure
Hospitalization
Medication
Resumen
Objetivos

Describir las características clínicas y el manejo terapéutico y determinar los eventos cardiovasculares tras un año de seguimiento en una población contemporánea con insuficiencia cardíaca (IC) con y sin diabetes tipo 2 en España. También se analizó en la población DAPA-HF (pacientes que cumplieron la mayoría de los criterios de inclusión del estudio DAPA-HF) y en los pacientes tratados basalmente con inhibidores SGLT2.

Métodos

Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La fecha índice fue 1 de enero de 2019. Se seleccionaron sujetos ≥ 18 años que recibieron tratamiento por IC en 2019. Se analizaron los eventos durante 2019.

Resultados

Se identificaron 21.851 pacientes con IC (78 ± 11,3 años; 53% varones; 50,9% IC con fracción de eyección reducida; 44,5% en clase funcional NYHA II). La prevalencia de IC fue del 1,88% y la incidencia 2,83 por 1.000 pacientes-año. El 66,1% tomaba inhibidores del sistema renina-angiotensina, el 69,4% betabloqueantes, el 31,2% antialdosterónicos y el 7,5% sacubitrilo/valsartán. Durante el año de seguimiento, el 29,8% fue hospitalizado por descompensación de la IC (tiempo medio primer evento 120,9 ± 72,5 días), un 12,3% murieron, un 8,1% murieron durante la hospitalización. Los eventos fueron más frecuentes en los pacientes con diabetes tipo 2. Las hospitalizaciones por IC fueron más comunes en la población similar a DAPA-HF.

Conclusiones

En España, la población con IC es anciana y tiene muchas comorbilidades. Aproximadamente la mitad de los pacientes tienen IC con fracción de eyección reducida. Existe margen de mejora en el manejo de la IC, en particular mediante el empleo de aquellos fármacos que reducen tanto la hospitalización por IC como la mortalidad, para disminuir la carga de IC.

Palabras clave:
DAPA-HF
Muerte
Insuficiencia cardíaca
Hospitalización
Medicación
Full Text
Introduction

Heart failure (HF) is a common yet very serious chronic cardiovascular condition1,2. The prevalence of HF is around 2% of the adult population in developed countries3,4. However, it is expected that prevalence will increase in coming years, mainly due to the aging of the population3,5.

HF is a progressive and debilitating condition that is associated with high mortality rates6. It is the leading cause of hospitalization in the United States and Europe7, and the risk of death in HF patients increases with each hospital admission8. Moreover, symptoms associated with HF have a negative impact on quality of life1,2,9.

Despite traditional HF therapies, including renin-angiotensin system inhibitors, beta blockers, and aldosterone antagonists, mortality and hospitalization rates remain unacceptably high10. However, in recent years, the PARADIGM-HF, and more recently the DAPA-HF and EMPEROR-Reduced trials have shown that sacubitril/valsartan and some SGLT-2 inhibitors, respectively, have a positive impact on morbidity and mortality among patients with HF and reduced left ventricular ejection fraction (HFrEF)11–13. As a result, new studies focusing on the current clinical profile and management of patients with HF and its impact on outcomes are warranted.

The aims of this study were to describe the epidemiology, clinical characteristics, and therapeutic management of the HF population in a current cohort of patients in Spain, stratified by the presence of type 2 diabetes (T2D), and to determine cardiovascular outcomes after one year of follow-up. This was also analyzed in a population that met the most relevant inclusion criteria for the DAPA-HF trial12 (DAPA-HF like population) and also in patients that were taking SGLT2 inhibitors at baseline for T2D.

Methods

Observational cohort study, comprising cross-sectional and longitudinal retrospective analyses using secondary data recorded in electronic health records from seven Spanish regions. Data sources were provided by the validated database BIG-PAC that is representative of the Spanish population14. BIG-PAC included data from primary health centers and referral hospitals within the Spanish national health system. Before exportation to BIG-PAC, data are rigorously anonymized and dissociated, making individual identification impossible15.

The index date (1st January 2019) was selected to characterize the most recent population since 2019 was the last full year at the time of protocol finalization. In this analysis, no significant differences were observed between the two years evaluated (2015 and 2019)16.

This study was approved by the Investigation Ethics Committee of Consorci Sanitari from Terrassa.

The HF population was defined as adults with at least one diagnosis of HF prior to the index date (1st January 2019). T2D was defined as adults who filled a prescription for any antidiabetic medication, with T2D diagnosis, or HbA1c > 7% prior to the index date. The DAPA-HF like population included those adults with a HF history > 8 weeks, standard HF treatment, NYHA class ≥ II within one year prior to the index date, and EF ≤ 40%. The SGLT-2 inhibitors population included those patients taking SGLT-2 inhibitors at baseline for T2D.

A search for comorbidities was made in all available data prior to the index date, with the exception of severe hypoglycemia which was considered only within one year before the index date, and cancer which was searched for up to five years prior to the index date. A minimum of one year of data before the index date was required. Comorbidities included ischemic heart disease, HF, chronic kidney disease (CKD), atrial fibrillation, stroke, peripheral artery disease, major organ specific bleeding, microvascular complications, severe hypoglycemia, keto-/lactate acidosis cancer, chronic obstructive pulmonary disease, and lower limb complications. ICD-9 and ICD-10 codes (https://eciemaps.mscbs.gob.es) were considered for the diagnosis of comorbidities (Appendix A Supplementary Table 1).

Treatment information was recorded from the registries for dispensing medicines according to the Anatomical Therapeutic Chemical Classification System (Appendix A Supplementary Table 1)17. HF treatments, warfarin, statins, antiplatelets, antihypertensive drugs, nitrates, and antidiabetic medications were recorded. The prescribing a drug in a specific patient was based only on medical criteria (routine practice).

Prevalence, incidence, and baseline characteristics (total HF population and by T2D status), including demographics, comorbidities, and medications, were calculated at the index date. Incidence was calculated as all newly diagnosed patients during the year of interest divided by the number of patients without HF in the population at the beginning of 2019. Prevalence was calculated as all patients with a HF diagnosis at the end of 2019 divided by all individuals in the total population.

Cardiovascular events were defined as a main diagnosis during a hospital visit or stay occurring at any time during 2019 after the index date (Appendix A Supplementary Table 1). All-cause death was defined as death of any cause. Cardiovascular events (myocardial infarction [MI], stroke, HF, CKD, defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 according to CKD-EPI, and peripheral artery disease [PAD]) were calculated in the overall HF, DAPA-HF, and SGLT2 inhibitors populations, according to the presence of T2D, and were stratified by age and gender.

The following variables were also assessed for the total HF group and by the presence of T2D: incidence and hospitalization rates, hospital readmission rates, mortality rates, mortality rates during hospitalization, and mortality rates after first hospitalization.

Statistical analysis

Categorical variables were described by their absolute (n) and relative frequencies (%) and continuous variables by mean and standard deviation. Event rates were presented as events per 1,000 patient-years. Categorical variables were compared with the Chi-squared test or Fisher’s exact test when appropriate. When two means were compared, Student’s t-test was used.

Analyses of events were performed for the index date of 1st January 2019 with one year of follow-up. Time to first event was analyzed with the contrast Student’s t-test for independent samples. A level of statistical significance of 0.05 was applied in all the statistical tests. The data were analyzed using the statistical package SPSS v25.0 (SPSS Inc., Chicago, Illinois, USA).

Results

At the index date, 21,851 patients with HF were analyzed (Fig. 1). HF incidence was 2.83 per 1,000 patient-years and prevalence 1.88%. T2D patients had a HF prevalence about 12-fold of those without T2D (16.2% vs 1.3%).

Figure 1.

Flowchart modern population (2019).

HF: heart failure.

*The HF population was defined as all patients ≥ 18 years of age and with at least one diagnosis of HF prior to the index date (1st January 2019).

(0.13MB).

The baseline clinical characteristics of the HF population according to the presence of T2D are presented in Table 1. Overall, mean age was 78.0 ± 11.3 years, and 50.9% of patients had HFrEF, 66.1% of patients were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. A total of 7,371 (33.7%) patients had T2D. Those patients with T2D had lower EF (42.8 ± 10.6% vs. 44.7 ± 10.7%; p < 0.001), were shifted towards worse NYHA functional classes (NYHA functional class iiiiv 46.9% vs. 38.2%; p < 0.001) and had more comorbidities (ischemic heart disease: 27.8% vs 18.8%; p < 0.001; CKD: 37.3% vs. 23.4%; p < 0.001; stroke: 13.3% vs. 9.8%; p < 0.001). Patients with T2D were taking more renin-angiotensin system inhibitors (70.5% vs. 63.9%; p < 0.001) and beta blockers (74.4% vs. 66.8%; p < 0.001), but less sacubitril/valsartan (5.8% vs. 8.3%; p < 0.001).

Table 1.

Baseline clinical characteristics of the heart failure population at index date 1st January 2019 according to the presence of type 2 diabetes.

  No T2D (n = 14,480; 66.3%)  T2D (n = 7,371; 33.7%)  Total HF (n = 21,851; 100%)  p 
Biodemographic data
Age, years  78.3 ± 11.8  77.4 ± 10.3  78.0 ± 11.3  0.001 
≥85 years, n (%)  5,827 (40.2)  3,157 (42.8)  8,984 (41.1)  <0.001 
Sex (male), n (%)  7,566 (52.3)  4,024 (54.6)  11,590 (53.0)  0.001 
Systolic blood pressure, mmHg  128.6 ± 23.4  131.7 ± 18.5  129.7 ± 21.9  < 0.001 
Heart failure data
NYHA functional class, n (%)
2,019 (13.9)  762 (10.3)  2,781 (12.7)   
II  6,569 (45.4)  3,147 (42.7)  9,716 (44.5)  <0.001 
III  5,067 (35)  3,105 (42.1)  8,172 (37.4)   
IV  464 (3.2)  357 (4.8)  821 (3.8)   
Left ventricular ejection fraction, %  44.7 ± 10.7  42.8 ± 10.6  44.0 ± 10.7  <0.001 
≤40%, n (%)  6,424 (50.0)  3,608 (52.6)  10,032 (50.9)  <0.001 
>40–<50%, n (%)  755 (5.9)  798 (11.6)  1,553 (7.9)  <0.001 
≥50%, n (%)  5,665 (44.1)  2,458 (35.8)  8,123 (41.2)  <0.001 
Laboratory data
eGFR, mL/min/1.73 m2  77.8 ± 20.1  72.5 ± 23.0  76.0 ± 21.3  <0.001 
HbA1c, %  5.1 ± 0.9  7.3 ± 1.8  7.2 ± 1.8  <0.001 
Comorbidities
Cardiovascular disease, n (%)
Ischemic heart disease  2,720 (18.8)  2,049 (27.8)  4,769 (21.8)  <0.001 
Myocardial infarction  1,732 (12.0)  1.398 (19.0)  3,130 (14.3)  <0.001 
CAGBG  196 (1.4)  184 (2.5)  380 (1.7)  <0.001 
PCI with stent  394 (2.7)  297 (4.0)  691 (3.2)  <0.001 
Unstable angina  576 (4.0)  458 (6.2)  1,034 (4.7)  <0.001 
Angina pectoris  1,022 (7.1)  713 (9.7)  1,735 (7.9)  <0.001 
Stroke  1,419 (9.8)  982 (13.3)  2,401 (11.0)  <0.001 
Ischemic stroke  1,073 (7.4)  765 (10.4)  1,838 (8.4)  <0.001 
Hemorrhagic stroke  73 (0.5)  49 (0.7)  122 (0.6)  0.132 
Transitory ischemic attack  387 (2.7)  274 (3.7)  661 (3.0)  <0.001 
Atrial fibrillation  4,742 (32.8)  2,504 (34.0)  7,246 (33.2)  0.070 
Peripheral artery disease  600 (4.1)  450 (6.1)  1,050 (4.8)  <0.001 
Chronic kidney disease  3,392 (23.4)  2,751 (37.3)  6,143 (28.1)  <0.001 
Microvascular complications  3.094 (42.0)  3,094 (14.2)  <0.001 
Diabetic mono-/polyneuropathy  508 (6.9)  508 (2.3)  <0.001 
Diabetic eye complications  2,117 (28.7)  2,117 (9.7)  <0.001 
Diabetic foot/ peripheral angiopathy  380 (5.2)  380 (1.7)  <0.001 
Diabetic kidney disease  655 (8.9)  655 (3.0)  <0.001 
Severe hypoglycemia  629 (8.5)  629 (2.9)  <0.001 
Keto-/lactose acidosis  55 (0.8)  55 (0.3)  <0.001 
Other comorbidities, n (%)
Cancer  1,534 (10.6)  883 (12.0)  2,417 (11.1)  0.002 
Chronic obstructive pulmonary disease  2,244 (15.5)  1,503 (20.4)  3,747 (17.2)  <0.001 
Lower limb amputations  36 (0.3)  115 (1.6)  151 (0.7)  <0.001 
Major organ specific bleeding  383 (2.7)  246 (3.3)  629 (2.9)  0.004 
Therapies
Heart failure medications, n (%)  14,480 (100)  7,371 (100)  21,851 (100)  – 
Renin-angiotensin system inhibitors  9,253 (63.9)  5,193 (70.5)  14,446 (66.1)  <0.001 
Angiotensin-converting enzyme inhibitors  4,421 (30.5)  2,419 (32.8)  6,840 (31.3)  0.001 
Angiotensin receptor blockers  4,832 (33.4)  2,774 (37.6)  7.606 (34.8)  <0.001 
Beta blockers  9,678 (66.8)  5,482 (74.4)  15,160 (69.4)  <0.001 
Loop-diuretics  10,018 (69.2)  5,662 (76.8)  15,680 (71.8)  <0.001 
Aldosterone antagonists  4,493 (31.0)  2,323 (31.5)  6,816 (31.2)  0.463 
Sacubitril/valsartan  1,202 (8.3)  430 (5.8)  1,632 (7.5)  <0.001 
Digoxin  1,105 (7.6)  571 (7.8)  1,676 (7.7)  0.762 
Other cardiovascular medication, n (%)
Low dose aspirin  2,947 (20.4)  2,230 (30.3)  5,177 (23.7)  <0.001 
Receptor P2Y12 antagonists  1,284 (8.9)  853 (11.6)  2,137 (9.8)  0.001 
Statins  7,325 (50.6)  4,573 (62.0)  11,898 (54.5)  <0.001 
Antihypertensives  2,709 (18.7)  1,892 (25.7)  4,601 (21.1)  <0.001 
Dihydropyridines CCB  1,641 (11.3)  1,434 (19.5)  3,075 (14.1)  <0.001 
Thiazides  835 (5.8)  379 (5.1)  1,214 (5.6)  0.057 
Non-dihydropyridines CCB  417 (2.9)  232 (3.2)  649 (3.0)  0.271 
Nitrates  1,477 (10.2)  934 (12.7)  2,411 (11.0)  <0.001 
Warfarin  2,685 (18.5)  1,411 (19.1)  4,096 (18.8)  0.283 
Diabetes medication, n (%)  6,733 (91.3)  6,733 (30.8)  <0.001 
Metformin  4,993 (67.7)  4,993 (22.9)  <0.001 
Sulfonylurea  2,560 (34.7)  2,560 (11.7)  <0.001 
DPP4 inhibitors  1,836 (24.9)  1,836 (8.4)  <0.001 
SGLT-2 inhibitors  797 (10.8)  797 (3.7)  <0.001 
GLP-1 receptor agonists  222 (3.0)  222 (1.0)  <0.001 
Metiglinides  389 (5.3)  389 (1.8)  <0.001 
Glitazones  77 (1.0)  77 (0.4)  <0.001 
Acarbose  113 (1.5)  113 (0.5)  <0.001 
Insulin  1,648 (22.4)  1,648 (7.5)  <0.001 

T2D: type 2 diabetes; HF: heart failure; eGFR: estimated glomerular filtration rate; CABG: coronary artery bypass graft; PCI: percutaneous coronary intervention; CCB: calcium channel blockers; DPP4: dipeptidyl peptidase 4; SGLT-2: sodium-glucose Cotransporter-2; GLP-1: glucagon-like peptide-1.

During the one year of follow-up, 29.8% of patients had HF decompensation leading to hospitalization, and 12.3% died. The event that occurred the earliest was CKD, followed by HF hospitalization. Event rates were more common among patients with T2D (all-cause death 14.1 vs. 12.6 events/100 patient-years, p = 0.004; myocardial infarction: 8.9 vs. 3.1 events/100 patient-years, p < 0.001; heart failure: 42.9 vs. 34.5 events/100 patient-years; p < 0.001; chronic kidney disease: 17.6 vs 8.6 events/100 patient-years; p < 0.001) (Table 2) and with age. Whereas mortality rates (13.6% vs. 11.1%; p < 0.001) and HF decompensation (30.8% vs. 28.9%; p = 0.002) were more common in women, MI (4.0% vs. 5.6%; p < 0.001) and PAD (1.4% vs. 2.6%; p < 0.001) were in men (Table 3).

Table 2.

Event rates after one year of follow-up.

  No T2D (n = 14,480; 66.3%)  T2D (n = 7,371; 33.7%)  Total HF (n = 21,851; 100%)  p 
All-cause death, n (%)  1,708 (11.8)  969 (13.2)  2,677 (12.3)  0.004 
Events per 100 patient-year  12.6  14.1  13.1   
Time for first event, days  178.7 ± 70.6  187.1 ± 69.1  181.8 ± 70.1  0.003 
Myocardial infarction, n (%)  442 (3.1)  618 (8.4)  1,060 (4.9)  <0.001 
Events per 100 patient-year  3.1  8.9  5.0   
Time for first event, days  132.3 ± 61.2  126.4 ± 72.5  128.8 ± 68.1  0.167 
Stroke, n (%)  466 (3.2)  299 (4.1)  765 (3.5)  0.001 
Events per 100 patient-year  3.3  4.2  3.6   
Time for first event, days  133.4 ± 83.2  115.6 ± 714.0  126.5 ± 79.1  0.002 
Hart failure, n (%)  4,070 (28.1)  2,442 (33.1)  6,512 (29.8)  <0.001 
Events per 100 patient-year  34.5  42.9  37.2   
Time for first event, days  124.3 ± 73.8  115.2 ± 70.0  120.9 ± 72.5  <0.001 
Chronic kidney disease, n (%)  1,180 (8.2)  1,154 (15.7)  2,334 (10.7)  <0.001 
Events per 100 patient-year  8.6  17.6  11.5   
Time for first event, days  117.2 ± 60.6  107.9 ± 60.1  112.6 ± 60.5  <0.001 
Peripheral artery disease, n (%)  224 (1.6)  221 (3.0)  445 (2.0)  <0.001 
Events per 100 patient-year  1.6  3.1  2.1   
Time for first event, days  129.2 ± 71.7  123.6 ± 66.2  126.4 ± 69.0  0.392 

HF: heart failure; T2D: type 2 diabetes.

Table 3.

Event rates after one year of follow-up by age groups and by gender.

  <40 years (n = 219; 1.0%)  40–54 years (n = 798; 3.7%)  55–64 years (n = 1,667; 7.6%)  65–74 years (n = 3,483; 15.9%)  75–84 years (n = 6,703; 30.7%)  ≥85 years (n = 8,981; 41.1%)  p  Women (n = 10,261; 47.0%)  Men (n = 11,590; 53.0%)  p 
All-cause death, n (%)  3 (1.4)  18 (2.3)  72 (4.3)  227 (6.5)  577 (8.6)  1,780 (19.8)  <0.001  1,395 (13.6)  1,282 (11.1)  <0.001 
Events per 100 patient-year  1.4  2.3  4.4  6.8  9.0  21.9    14.6  11.7   
Myocardial infarction, n (%)  2 (0.9)  16 (2.0)  71 (4.3)  170 (4.9)  331 (4.9)  470 (5.2)  <0,001  415 (4.0)  645 (5.6)  <0.001 
Events per 100 patient-year  0.9  2.0  4.4  5.0  5.1  5.4    4.2  5.8   
Stroke, n (%)  2 (0.9)  14 (1.8)  54 (3.2)  113 (3.2)  249 (3.7)  333 (3.7)  0.012  338 (3.3)  427 (3.7)  0.117 
Events per 100 patient-year  0.9  1.8  3.3  3.3  3.8  3.8    3.4  3.8   
Heart failure, n (%)  19 (8.7)  136 (17.0)  442 (26.5)  1,015 (29.1)  2,090 (31.2)  2,810 (31.3)  <0.001  3,163 (30.8)  3,349 (28.9)  0.002 
Events per 100 patient-year  9.2  19.1  32.1  36.1  39.4  39.7    38.8  35.8   
Chronic kidney disease, n (%)  3 (1.4)  35 (4.4)  84 (5.0)  293 (8.4)  757 (11.3)  1,162 (12.9)  <0.001  1,089 (10.6)  1,245 (10.7)  0.758 
Events per 100 patient-year  1.4  4.5  5.2  8.9  12.3  14.2    11.5  11.6   
Peripherial artery disease, n (%)  4 (0.5)  30 (1.8)  67 (1.9)  144 (2.2)  200 (2.2)  0.005  142 (1.4)  303 (2.6)  <0.001 
Events per 100 patient-year  0.5  1.8  2.0  2.2  2.3    1.4  2.7   

Regarding hospitalization outcomes, hospitalization rates reached 30.9%, and 8.1% of patients died during hospitalization. Hospitalization rates and mortality rates during hospitalization were more common in patients with T2D (incidence and hospitalization: 34.0% vs. 29.3%; p < 0.001; mortality: 13.2% vs. 11.8%; p = 0.004) (Table 4).

Table 4.

Hospitalization outcomes after one year of follow-up.

  No T2D (n = 14,480; 66.3%)  T2D (n = 7,371; 33.7%)  Total HF (n = 21,851; 100%)  p 
Incidence and hospitalization rate, n (%)  4,243 (29.3)  2,507 (34.0)  6,750 (30.9)  <0.001 
Mortality rates, n (%)  1,708 (11.8)  969 (13.2)  2,677 (12.3)  0.004 
Mortality rates during hospitalization, n (%)  1,109 (7.7)  663 (9.0)  1,772 (8.1)  0.001 
Mortality rates after hospitalization, n (%)  599 (4.1)  306 (4.2)  905 (4.1)  0.959 

HF: heart failure; T2D: type 2 diabetes.

A specific analysis was performed in the DAPA-HF like population (n = 4,243). In this subpopulation, mean age was 78.0 ± 11.0 years, and all patients had HFrEF. Most patients were designated as NYHA functional class ii (49.7%) or iii (45.4%). A total of 1,699 (40.0%) patients had T2D. Some 98.2% of patients were taking renin-angiotensin system inhibitors, 100% beta blockers, 20.0% aldosterone antagonists, and 3.7% sacubitril/valsartan. Compared with patients without T2D, those with T2D were taking more sacubitril/valsartan and digoxin (Appendix A Supplementary Table 2).

During the one year of follow-up, 50.3% of patients had HF decompensation leading to hospitalization, and 12.2% died. The event that occurred the earliest was also CKD followed by hospitalization due to HF. Event rates were more common among patients with T2D (Appendix A Supplementary Table 3) and mortality, HF and renal outcomes with age (Appendix A Supplementary Table 4). Whereas HF decompensation was more common in women, MI and PAD in were so in men (Appendix A Supplementary Table 5).

A specific analysis was performed in the SGLT2 inhibitors population (n = 797). In this subpopulation, mean age was 72.6 ± 11.3 years, and 46.8% of patients had HFrEF. The majority of patients were in NYHA functional class ii (40.5%) or iii (42.4%). All patients had T2D. A total of 68.9% of patients were taking renin-angiotensin system inhibitors, 72.5% beta blockers, 46.8% aldosterone antagonists, and 3.6% sacubitril/valsartan (Appendix A Supplementary Table 6).

During the one year of follow-up, 36.4% of patients had HF decompensation leading to hospitalization, and 19.0% died (Appendix A Supplementary Table 7). Mortality increased with age (Appendix A Supplementary Table 8). HF and PAD rates were more frequent in men (Appendix A Supplementary Table 9).

Discussion

In our study, HF incidence was 2.8 per 1,000 patient-years and the prevalence 1.9%. Of note, the presence of T2D greatly increased the risk of having HF. Despite previous studies performed in Spain having shown a higher prevalence of HF, our data were in line with numbers reported in Europe and the United States10,18–20. On the other hand, our study showed that 51% of patients had HFrEF, in accordance with previous studies21,22.

Regarding HF treatments, our study showed that there is much room for improvement. Prescribing HF guideline-recommended therapies is essential to improving functional class, but more importantly for reducing HF hospitalizations and mortality1,2,21,23. Unfortunately, while patients included in specific HF units exhibit higher use of evidence-based HF medications24, the vast majority of the studies performed in other clinical settings have shown lower prescribing rates25–27.

Of note, lower prescribing of HF guideline-recommended drugs increases the use of healthcare resources, particularly first and recurrent hospitalizations28. By contrast, increased adherence to HF drugs improves clinical outcomes29. In addition, after one year of follow-up, the main complication was HF hospitalization, emphasizing the importance of prescribing those drugs that have demonstrated a beneficial effect not only on mortality, but also on morbidity1,2.

In our study, 12% of the HF patients died during follow-up. Although the prognosis of HF has improved in recent decades10,30, mortality rates remain high10. A recent meta-analysis estimated 1, 5 and 10-year survival to be 87%, 57%, and 35%, respectively, among HF patients. Of note, mortality was lowest in secondary care studies, suggesting that specialist care, together with better HF treatment, improves survival compared to primary care31.

Regarding hospitalization outcomes, 8% of patients died during HF hospitalization. Mortality rates during hospitalization were higher in T2D patients. It has been estimated that 30-day mortality ranges from 5% to 20%10,32. Most noticeably, HF hospitalization is an independent predictor for increased HF mortality10,33. Moreover, HF hospitalization cost is the main driver to the total health care cost for the HF population5,34. Importantly, it is expected that absolute numbers of HF hospitalizations will increase in the following years due to the aging of the population10.

The PARADIGM-HF trial showed that, compared with enalapril, sacubitril/valsartan significantly reduced the risk of HF hospitalization11 and in the DAPA-HF trial, dapagliflozin significantly reduced the risk of a first worsening HF event12. A recent study has shown that compared with standard therapy, early comprehensive disease-modifying pharmacological therapy with sacubitril/valsartan, beta blockers, aldosterone antagonists, and dapagliflozin is associated with a significant reduction in cardiovascular death or HF hospital admission by 62%35. As a result, prescribing drugs that decrease both HF hospitalizations and mortality are mandatory to reduce HF burden.

In our study, patients with T2D had more comorbidities, as well as more cardiovascular and renal outcomes, compared to patients without T2D. This is in line with data from the RICA registry which showed that T2DM was a common condition among patients hospitalized for HF and its presence was an independent predictor for all-cause mortality and HF readmission36.

Remarkably, HF is an early complication of T2D patients37. In addition, many patients with T2D patients have asymptomatic left ventricular dysfunction in the first years after their diabetes diagnosis38. As a result, early treatment of patients with T2D with SGL2 inhibitors may delay or even prevent the development of HF39,40. In the SGLT2 inhibitors population, although the proportion of patients taking aldosterone antagonists was higher than in the overall HF population, around one third of patients were not taking renin-angiotensin system inhibitors, and nearly 30% beta blockers, and this translated to high rates of HF hospitalization and death. Of note, mortality rates were higher in the SGLT2 inhibitors population than in the T2D HF and the DAPA-HF like populations, suggesting not only a worse clinical profile with more comorbidities and a worse functional class, but also a late use of these drugs despite their proven benefits for cardiovascular outcomes12,40.

In the DAPA-HF like population, although almost all patients were taking renin-angiotensin system inhibitors and beta blockers, 50% of patients experienced HF decompensation and 12% died. As a result, it is mandatory to optimize cardioprotective medication prescribing in order to reduce HF outcomes39. In fact, it has recently been suggested that it may be more important to prioritize drug initiation before dose titration for patients with HFrEF41.

Cardiovascular and renal outcomes significantly increased with age, and previous studies have also shown a high risk of complications in elderly patients with HF42,43. Chiefly, elderly patients benefit from evidence-based HF medications44,45. As a result, HF treatment should be optimized in this population as well, however with caution.

Limitations

This was an observational retrospective cohort study that used secondary data from electronic health records. These studies have some limitations, and, as a result, only indirect causality can be provided. Additionally, due to the retrospective design of the study, some relevant data could not be recorded. Moreover, the absence of patient classification according to EF makes it more difficult to extrapolate treatment patterns by EF groups.

However, the large number of patients and the robustness of the data may make it possible to determine the value of the study. On the other hand, although data came from only seven Spanish regions, previous studies have shown that these data are representative of the Spanish population14.

Conclusions

In Spain, the HF population is old, have many comorbidities, and approximately half of patients have HFrEF. Patients with T2D have more comorbidities, as well as more cardiovascular and renal outcomes, compared to patients without T2D. Unfortunately, a significant proportion of patients are not taking evidence-based HF medications, which translates to higher outcome rates, particularly HF decompensation. This occurs in patients with and without T2D.

Therefore, improving HF management, particularly through the use of drugs that reduce HF hospitalization and mortality, is fundamental to decreasing the HF burden.

Funding

This study was funded by AstraZeneca. The funding body played no role in the design, data collection, analysis, interpretation or writing of the manuscript.

Conflicts of interest

The authors declare that they do not have any conflicts of interest.

Appendix A
Supplementary data

The following is Supplementary data to this article:

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Please cite this article as: Escobar C, Varela L, Palacios B, Capel M, Sicras-Mainar A, Sicras-Navarro A, et al. Características clínicas, manejo y riesgo de complicaciones a un año en pacientes con insuficiencia cardíaca con y sin diabetes tipo 2 en España. Rev Clin Esp. 2022;222:195–204.

Copyright © 2021. Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)
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