Physicians' Academy for Cardiovascular Education

Combination of ARNI, BB, MRA, and SGLT2i most effective in reducing outcomes in HFrEF

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

Literature - Tromp J, Ouwerkerk W, Van Veldhuisen DJ et al. - JACC Heart Fail. 2022 Feb;10(2):73-84. doi: 10.1016/j.jchf.2021.09.004.

Introduction and methods

Aim of the study

A systematic network meta-analysis was performed to estimate and compare the effects of combinations of different pharmacological therapies for HFrEF.


Randomized clinical trials that investigated the treatment effects of digoxin, isosorbide dinitrate and hydralazine (H-ISDN), ACEi, ARB, BB, MRA, ivabradine, ARNI, SGLT2i, vericiguat, or omecamtiv-mecarbil in adult patients with HFrEF in an outpatient setting or after stabilization after HF hospitalization were considered for inclusion. A total of 75 trials, with a total of 95,444 participants (23% women) were included in the analysis.


The primary outcome was all-cause death. Secondary outcomes were a composite of CV death and hospitalization for HF, CV death, and likelihood of drug discontinuation. In a secondary analysis, number of life-years gained was estimated in the BIOSTAT-CHF and ASIAN-HF populations (1-3).

Main results

All-cause mortality

Composite of CV death and hospitalization for HF

CV death

Drug discontinuation

Estimated life-years gained


This meta-analysis showed that ARNI, BB, MRA, and SGLT2i was the most effective treatment combination in reducing all-cause death, the composite outcome of CV death and HF hospitalization, and CV death alone in patients with HFrEF.

The authors of the article wrote: “The substantial combined survival benefit of comprehensive therapy for HFrEF compared to single pharmacological agents, advocates for early initiation of comprehensive treatment over sequencing of single agents with titration to target dosages.”


Show references

Find this article online at JACC Heart Fail.

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