GLP-1 Receptor Agonists in Heart Failure: A Systematic Review and Meta-analysis with Phenotype-Specific Effects and Dual Analytical Frameworks.
Yahui Yuan, Chun Chen, Xiuming Li et al.
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In 30 seconds
This systematic review and random-effects meta-analysis assessed GLP-1 receptor agonists across heart-failure phenotypes and trial types, including 14 trials and 15,882 patients with heart failure. In phenotype-based analyses, treatment was associated with lower risks in HFpEF of major adverse cardiovascular events (HR 0.79; 95% CI 0.66-0.94), hospitalization for heart failure (HR 0.48; 95% CI 0.27-0.85), and other reported outcomes. In HFrEF, most assessed outcomes were not significantly reduced, although cardiovascular death was lower (HR 0.71; 95% CI 0.54-0.95). Benefits were concentrated in HF subgroups from cardiovascular outcome trials and in overweight or obese patients with HFpEF.
Key findings
- In HFpEF, GLP-1 RAs were associated with reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010) and HF hospitalization (HR 0.48; 95% CI 0.27-0.85; p = 0.012).
- In HFpEF, all-cause mortality was lower (HR 0.75; 95% CI 0.62-0.89; p = 0.001), as was the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013).
- In HFrEF, no significant reductions were observed for MACE, HF hospitalization, the composite outcome, or all-cause mortality; cardiovascular death was reduced (HR 0.71; 95% CI 0.54-0.95; p = 0.019).
- In HF subgroups from cardiovascular outcome trials, GLP-1 RAs were associated with lower MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001).
Why it matters
The findings suggest that the relationship between GLP-1 RA treatment and heart-failure outcomes may differ by ejection-fraction phenotype. The more consistent HF-related signals in HFpEF, alongside limited evidence in HFrEF, underscore the importance of interpreting pooled results by phenotype rather than treating heart failure as a single population. The review also reports improved functional capacity and quality of life in HFpEF.
What to keep in mind
The evidence combines heterogeneous trial populations and designs, including HF subgroups from cardiovascular outcome trials; the authors identify the need for dedicated randomized trials, particularly in HFrEF.