Network Meta-Analysis of Quality of Life in Heart Failure With Reduced Ejection Fraction

BACKGROUND: Although the effects of various combinations of treatments on mortality and morbidity outcomes in heart failure with reduced ejection fraction (HFrEF) have been evaluated, the impact on quality of life is unknown. This study evaluated and compared the composite impact of pharmacological therapies on quality of life in HFrEF using a frequentist network meta-analysis and systematic review methodology. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1, 2021 and August 10, 2024. We included all contemporary and efficacious HFrEF therapies used in adults. The primary outcome was change in quality of life measured through the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire, expressed as mean difference (MD). RESULTS: We identified 41 randomized controlled trials representing 41 145 patients (76.5% male). The trials had a median of 276 participants (105–464), a mean left ventricular ejection fraction of 28%, and a median follow-up time of 5 months (3–8). A combination of angiotensin receptor blocker/neprilysin inhibitors (ARNi)+β-blockers (BB)+sodium-glucose cotransporter 2 inhibitors (SGLT2i; MD, +5.3 [+0.4, +10.3]) was the most effective at improving quality of life followed by ARNi+BB+mineralocorticoid receptor antagonists (MRA)+SGLT2i (MD, +7.1 [−1.0 to +15.2]), ACE inhibitor+BB+MRA+SGLT2i (MD, +5.3 [−2.6, to +13.3]), and ACE inhibitor+BB+MRA+ivabradine (MD, +5.2 [−3.1 to +13.6]), which were not statistically significant. Individually, the most effective treatments for improving quality of life were SGLT2i (MD, +3.4 [+1.4 to +5.30]), ivabradine (MD, +3.3 [+0.1 to +6.4]), ARNi (MD, +2.6 [−3.2 to +8.5]), and MRA (MD, +1.8 [−4.8 to +8.4]). CONCLUSIONS: A composite of ARNi+BB+SGLT2i or ARNi+BB+MRA+SGLT2i was the most effective at improving quality of life in patients with HFrEF.