The most effective combination of pharmacological therapy for heart failure with reduced ejection fraction: a network meta-analysis of randomized controlled trials

• Published in: BMC cardiovascular disorders 2024-11, Vol.24 (1), p.666-15, Article 666
• Main Authors: Tang, Huilin, Germinal, Kimberly, Milfort, Alexandra, Chen, Wei-Han, Chang, Shao-Hsuan, Huang, Wenxi, Li, Yujia, Lu, Ying, Ahmed, Mustafa M, Kimmel, Stephen E, Bian, Jiang, Guo, Jingchuan
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Angiotensin; Angiotensin-converting enzyme inhibitors; Bias; Cardiovascular agents; Cardiovascular Agents - adverse effects; Cardiovascular Agents - therapeutic use; Cardiovascular disease; Cause of Death; Clinical trials; Congestive heart failure; Death; Diabetes; Disease prevention; Dosage and administration; Drug therapy; Drug Therapy, Combination; Ejection fraction; Female; Glucose transporter; Heart failure; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - mortality; Heart Failure - physiopathology; Heart failure with reduced ejection fraction; Hospitalization; Humans; Male; Meta-analysis; Methods; Middle Aged; Mineralocorticoid Receptor Antagonists - therapeutic use; Mineralocorticoid receptors; Morbidity; Mortality; Network Meta-Analysis; Patient outcomes; Peptidyl-dipeptidase A; Pharmacological interventions; Randomized controlled trials; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Stroke Volume - drug effects; Treatment Outcome; Ventricular Function, Left - drug effects
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-024-04339-3

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. 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. 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). 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.