AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
GLP-1 Receptor Agonists in Older Adults with Heart Failure: A Systematic Review and Meta-Analysis with Trial Sequential Analysis
By Miyashita S, Tanji A, Minami K
Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated cardiovascular benefit in selected populations and are increasingly evaluated in heart failure (HF). However, evidence regarding their efficacy in older adults with HF remains limited, despite the high burden of HF events, multimorbidity, and impaired health status in this population. Therefore, we assessed the clinical impact of GLP-1 receptor agonists in older patients with chronic HF. Methods: We performed a systematic search of multiple databases to identify randomized controlled trials and observational studies comparing GLP-1 receptor agonists versus comparator in older adults, defined as aged ≥65 years, with chronic HF. We extracted hazard ratios (HRs) for trial-defined time-to-event clinical outcomes and pooled results using a random-effects model with Hartung-Knapp adjustment. The primary outcome was a composite of cardiovascular mortality and HF exacerbation. Age-stratified effects were synthesized for older adults versus younger adults as reported in each study, and subgroup differences were evaluated using an interaction test. Results: A total of 7 studies, including 6 randomized controlled trials and 1 observational study, involving a total of 20,847 patients were included in the final analysis. Follow-up duration ranged from 52 weeks to 47.5 months across the included studies. Among older adults, GLP-1-based therapies were associated with a lower risk of the composite clinical endpoint compared with control (HR, 0.66; 95% CI, 0.52-0.85, I ² =6.3%), with no evidence of treatment interaction by age (P for subgroup difference=0.80). GLP-1-based therapies also improved KCCQ-CSS in older adults (mean difference, 7.49 points; 95% CI, 5.22-9.76), with no significant difference compared with younger adults (P for subgroup difference=0.89). In drug-specific subgroup analyses among older adults, treatment effects differed by agent, with a greater estimated benefit for tirzepatide (HR, 0.57; 95% CI, 0.36-0.90) than semaglutide (HR, 0.74; 95% CI, 0.54-1.03; P for subgroup difference<0.0001). Trial sequential analysis confirmed firm evidence for the reduction in the primary outcome in older adults. Conclusions: In this systematic review and meta-analysis of randomized and observational evidence in chronic HF, GLP-1-based therapies were associated with improved clinical outcomes and health status in older adults. There was no evidence that the treatment benefit was attenuated compared with younger patients. The consistency of clinical and patient-reported findings, together with sufficient information size on trial sequential analysis, supports the robustness of GLP-1-based therapies in older adults with HF.