A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction.

OBJECTIVES

This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction.

BACKGROUND

The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized.

METHODS

We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]).

RESULTS

We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses.

CONCLUSIONS

In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.

Informations de copyright

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures Dr Tromp is supported by the National University of Singapore Start-up Grant; and has received consultancy fees from Olink proteomics and Roche Diagnostics; and served as a scientific advisor and shareholder of Us2.ai. Dr Richards has received consultancy/advisory board/speaker fees, research grants, and/or support in kind from Roche Diagnostics, Abbott Laboratories, Thermo Fisher, AstraZeneca, Novartis, Medtronic, and Boston Scientific. Dr van der Meer has received consultancy and/or research grants from Vifor Pharma, AstraZeneca, Servier, Novartis, Pfizer, and Ionis. Dr Anand has received consultancy fees from Amgen, ARCA, AstraZeneca, Boehringer Ingelheim, Boston Scientific, LivaNova, Novartis, Rockwell Medical, and Zensun. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the advisory board/steering committee/executive committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research and Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global LLC, Radcliffe Group Ltd, and Corpus; and serves as cofounder and non-executive director of Us2.ai. Dr Voors has received consultancy fees and/or research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novartis, Novo Nordisk, and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.