Key result
Combining ARNi, beta-blockers, and SGLT2 inhibitors drives a leading ~5-point QoL improvement in HFrEF.
Why the study?
While the effect of treatment combinations on mortality and morbidity in HFrEF has been evaluated, the impact on quality of life was unknown.
Do various combinations of pharmacological therapies improve quality of life in adults with HFrEF?
Meta-Analysis (n=41,145)
Yes
Do various combinations of pharmacological therapies improve quality of life in adults with HFrEF?
Effect estimate: MD 5.33 (95% CI 0.40-10.25)
A network meta-analysis suggests that combinations of guideline-directed medical therapies, particularly ARNi + BB + SGLT2i, significantly improve quality of life in patients with HFrEF.
Supports ARNi+BB+SGLT2i for QoL gains in HFrEF; extends GDMT evidence to patient-reported outcomes.
Background While the effect 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 1987 - August 2024. We included all contemporary and efficacious HFrEF therapies used in adults. The primary outcome was the mean change in QoL score 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 41145 patients which had a median of 276 (IQR 105, 464) participants who were mostly male (76.5%) with a mean left ventricular ejection fraction of 28%, and a median follow up time of 5 months (IQR 3,8). The combinations which resulted in the greatest improvement of quality of life were ARNi + BB + MRA + SGLT2i [MD 7.11 (95% CI -0.99-15.22)], which did not have a statistically significant effect, followed by ARNi + BB + SGLT2i [MD 5.33 (95% CI 0.40-10.25)], ACEi + BB + MRA+ SGLT2i [MD 5.32 (95% CI -2.63-13.26)], ACEi + BB + MRA + ivabradine [MD 5.24 (95% CI -3.07-13.55)]. Individually, the treatments which led to the greatest improvement in quality of life were H-ISDN [MD 3.87 (95% CI, -0.73 to 8.47)], which did not have a statistically significant effect, followed by SGLT2i [MD 3.37 (95% CI 1.44-5.30)], ivabradine [MD 3.26 (95% CI 0.08-6.43)], ARNi [MD 2.62 (95% CI -3.24-8.47)] and vericiguat [MD 1.00 (95% CI -3.18-5.18)]. Conclusion A composite of ARNi + BB + MRA + SGLT2i or ARNi + BB + SGLT2i was the most effective at improving quality of life in patients with HFrEF.
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Margaryan et al. (2025) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF) (n=41,145). ARNi + BB + SGLT2i vs. Placebo or other active treatments was evaluated on Mean change in QoL score (KCCQ Overall Summary Score and MLHFQ Overall score) (MD 5.33, 95% CI 0.40-10.25). The combination of ARNi, beta-blockers, and SGLT2 inhibitors had the largest statistically significant effect on improving quality of life in patients with HFrEF (MD 5.33).
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