Key result
The combination of ACEI, BB, MRA, and SGLT2i was the most effective therapy for reducing all-cause mortality in HFrEF patients.
Why the study?
Evidence for pharmacological therapies in HFrEF is growing, but there is no consensus on the most effective combination of pharmacological treatment.
Does combination pharmacological therapy reduce all-cause death, CV death, and hospitalization for heart failure in adults with HFrEF?
Meta-Analysis (n=90,529)
Does combination pharmacological therapy reduce all-cause death, CV death, and hospitalization for heart failure in adults with HFrEF?
The combination of ACEI, BB, MRA, and SGLT2i is the most effective pharmacological therapy for reducing all-cause mortality in patients with HFrEF.
Answers are grounded in this paper and cite their sources.
Quadruple GDMT should be prioritized in HFrEF; confirms superiority of ACEI/BB/MRA/SGLT2i over other combinations.
BACKGROUND: Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF. METHODS: We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments. RESULTS: We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32-0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12-0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18-0.39). CONCLUSION: This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy.
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Tang et al. (2024) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF) (n=90,529). Combination pharmacological therapies (ACEI, BB, MRA, SGLT2i, Vericiguat, Ivabradine) was evaluated on All-cause death (RR 0.46, 95% CI 0.32-0.66). The combination of ACEI, BB, MRA, and SGLT2i was the most effective therapy for reducing all-cause mortality in HFrEF patients.
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