Introduction and Objective: To evaluate and compare the therapeutic effects of current agents for heart failure with preserved ejection fraction (HFpEF).Methods: Literature retrieval was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov between inception and December 2024. Randomized controlled trials (RCTs) in patients with HFpEF, which intercompared current therapeutic agents and reported the cardiovascular outcomes were included. Network meta-analyses regarding these studies were implemented.Results: A total of 17 RCTs with 52,934 participants were included. Compared with non-users, GLP-1/GIP dual receptor agonists, GLP-1RA, SGLT-2i, MRA, and ARNI were all associated with reduced risk of the composite outcome of worsening heart failure and cardiovascular death in patients with HFpEF. The surface under the cumulative ranking curve (SUCRA) evaluation conferred a rank order as GLP-1/GIP dual agonists> GLP-1RA > SGLT-2i > MRA > ARNI in terms of the risk reduction in the composite cardiovascular outcome. Meanwhile, compared with non-users, GLP-1/GIP dual receptor agonists and MRA were all associated with significantly improved score of Kansas City Cardiomyopathy Questionnaire (KCCQ). And the corresponding rank order of SUCRA was GLP-1/GIP dual agonists> MRA > SGLT-2i > GLP-1RA.Conclusion: Compared with non-users, GLP-1/GIP dual receptor agonists, GLP-1RA, SGLT-2i, MRA and ARNI were associated with reduced risk of worsening heart failure and cardiovascular death in patients with HFpEF. Moreover, patients receiving GLP-1/GIP dual receptor agonists and MRA were with significantly improved score of KCCQ. GLP-1/GIP dual receptor agonists may serve as promising candidates in HFpEF treatment with exceptional cardiovascular benefits.
Z. Li: None. C. Lin: None. X. Cai: None. F. Lyu: None. W. Yang: None. L. Ji: None.
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