Original article
Changes in causes of death and influence of therapeutic improvement over time in patients with heart failure and reduced ejection fractionCambio en la causa de muerte e influencia de la mejora terapéutica con el tiempo en pacientes con insuficiencia cardiaca y fracción de eyección reducida

https://doi.org/10.1016/j.rec.2019.09.030Get rights and content

Abstract

Introduction and objectives

In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice.

Methods

This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n = 641, period: 2003-2004) and REDINSCOR I (n = 1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee.

Results

Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P < .001), mineralocorticoid antagonists (64% vs 44%; P < .001), implantable cardioverter-defibrillators (19% vs 2%; P < .001), and resynchronization therapy (7.2% vs 4.8%; P = .04). In these patients, sudden cardiac death was less frequent than in those in MUSIC (6.8% vs 11.4%; P < .001). After propensity score matching, we obtained 2 comparable populations differing only in treatments (575 vs 575 patients). In patients in REDINSCOR I, we found a lower risk of total mortality (HR, 0.70; 95%CI, 0.57-0.87; P = .001) and sudden cardiac death (sHR, 0.46; 95%CI, 0.30-0.70; P < .001), and a trend toward lower mortality due to end-stage HF (sHR, 0.73; 95%CI, 0.53-1.01; P = .059), without differences in other causes of death (sHR, 1.17; 95%CI, 0.78-1.75; P = .445), regardless of functional class.

Conclusions

In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Resumen

Introducción y objetivos

En pacientes con insuficiencia cardiaca y fracción de eyección reducida (IC-FEr), se ha demostrado en ensayos clínicos que diferentes terapias reducen la mortalidad, pero hay pocos datos de la práctica real acerca del efecto en los distintos tipos de muerte.

Métodos

Se estudió a 2.351 pacientes ambulatorios con IC-FEr (FE < 40%) procedentes de los registros prospectivos multicéntricos MUSIC (n = 641, años 2003-2004) y REDINSCOR I (n = 1.710, años 2007-2011). Las variables se registraron a la inclusión, y el seguimiento fue de 4 años. Un comité independiente adjudicó la mortalidad y sus causas.

Resultados

Los pacientes en el registro más contemporáneo recibieron con mayor frecuencia bloqueadores beta (el 85 frente al 71%; p < 0,001), antialdosterónicos (el 64 frente al 44%; p < 0,001), desfibrilador automático implantable (el 19 frente al 2%; p < 0,001) y resincronización (el 7,2 frente al 4,8%; p = 0,04). La población más contemporánea presentó menos muerte súbita (el 6,8 frente al 11,4%; p < 0,001). Tras emparejar por puntuación de propensión, se obtuvieron 2 poblaciones comparables que solo diferían en los tratamientos (575 frente a 575 pacientes): la población más contemporánea presentó menor riesgo de muerte total (HR = 0,70; IC95%, 0,57-0,87; p = 0,001) y de muerte súbita (sHR = 0,46; IC95%, 0,30-0,70; p < 0,001), con una tendencia de muerte por IC (sHR = 0,73; IC95%, 0,53-1,01; p = 0,059) y sin diferencias por otras causas (sHR = 1,17; IC95%, 0,78-1,75; p = 0,445), independientemente de la clase funcional.

Conclusiones

En pacientes ambulatorios con IC-FEr, la mejora terapéutica se asoció con un menor riesgo de muerte, principalmente debido a la significativa reducción de las muertes súbitas.

Section snippets

INTRODUCTION

Current therapeutic care of patients with acute heart failure (HF) is based on left ventricular ejection fraction (LVEF). In patients with reduced LVEF (< 40%), drug-based neurohormonal blocking and the use of devices have been proven to have well-established beneficial effects on mortality.1, 2 Additionally, beta-blockers and implantable cardioverter-defibrillators (ICDs) have been specifically shown to reduce sudden cardiac death, whereas angiotensin-converting enzyme inhibitors (ACEIs) (or

Study population and design

A total of 2351 patients with LVEF < 40% were included in 2 prospective cohorts from 2 multicenter longitudinal registries of outpatients with chronic HF. The MUSIC registry was designed to evaluate predictors of the risk of cardiac mortality and sudden cardiac death.12 This registry included 992 consecutive outpatients who came to specialized HF clinics at 8 Spanish teaching hospitals between April 2003 and December 2004. All patients had chronic symptomatic HF (New York Heart Association

Study population and mortality

The analysis included 2351 patients with LVEF < 40% from the MUSIC (n = 641, period: 2003-2004) and REDINSCOR I registries (n = 1710, period: 2007-2011). The differences between the 2 registries are listed in table 1. In particular, patients from REDINSCOR I had a higher risk profile, with a higher percentage of diabetes, worse NYHA functional class, higher heart rate, lower LVEF, higher prevalence of mitral regurgitation, higher NT-proBNP concentration, and lower hemoglobin concentration. Only the

DISCUSSION

The present study, based on clinical practice registries with well-described cohorts, has shown that the use of treatment based on therapies with proven benefits and recommended in clinical practice guidelines is linked to lower mortality, in particular the risk of sudden cardiac death, regardless of functional class.

CONCLUSIONS

In patients with HF and reduced ejection fraction, improved evidence-based medical treatment is associated with a decrease in deaths in clinical practice registries, mainly due to a significantly lower risk of sudden cardiac death regardless of functional class. These results confirm the need for strategies to encourage the inclusion of evidence-based treatments in clinical practice.

FUNDING

This study was partially funded by the Carlos III Health Institute, Madrid, Spain (RD12/0042/0049) (PI14/01637; INT16/00172) and by FEDER funds (CIBER Cardiovascular; CB16/11/00385).

CONFLICTS OF INTEREST

None related to this study.

WHAT IS KNOWN ABOUT THE TOPIC?

  • Based on decreased mortality rates observed in clinical trials, treatments have been recommended for patients with HF and reduced LVEF.

  • There is a paucity of data on actual use in clinical practice and on the effects on the various causes of death.

WHAT DOES THIS STUDY ADD?

  • In real-world clinical practice, the use of evidence-based therapies for patients with HF and reduced LVEF is associated with a lower risk of mortality.

  • The improvement in survival was mainly due to the significantly reduced

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