基于胰高血糖素样肽-1（GLP-1）的疗法用于肥胖相关射血分数保留的心力衰竭：一项纳入更广泛心力衰竭与心脏代谢证据的伞状综述。
完整摘要 · 中文译文
背景：肥胖相关射血分数保留型心力衰竭（HFpEF）的心脏代谢表型在临床中的患病率日益增加。现有系统评价和荟萃分析主要汇总了基于胰高血糖素样肽-1（GLP-1）疗法的疗效估计值，但由于尚未系统评估方法学局限性及原始试验的重叠情况，这些综合结果的可靠性和独立性仍不确定。因此，本伞状评价旨在评估现有评价层面证据的方法学质量、重叠程度、一致性和稳健性，而非再生成另一项疗效综合结果。 方法：我们开展了一项伞状评价，纳入评估GLP-1治疗方案在肥胖相关HFpEF及相邻心脏代谢人群中应用的系统评价、荟萃分析和网络荟萃分析。检索了PubMed、Embase、Web of Science和Cochrane图书馆过去十年的文献。以系统评价或荟萃分析为分析单位。采用AMSTAR 2评估方法学质量，并使用校正覆盖面积（CCA）量化各评价中原始研究的重叠程度。未进行新的荟萃分析；原始试验仅用于评估重叠并计算CCA。评价层面的结果根据效应方向、一致性、精确度、样本量、方法学质量、临床相关性和重叠程度进行综合。 结果：共对17项系统评价进行了定性分析，其中11项报告了与本评价相关的定量估计值。 核心综述层面的综合。对于心力衰竭住院，Diallo 等人的综述报告 HR 0.78（95% CI 0.73-0.84；n = 25,440）。对于心血管死亡和心力衰竭住院的复合终点，Diallo 等人报告 HR 0.84（95% CI 0.78-0.89），Ahmed HM 等人报告 HR 0.76（95% CI 0.64-0.90），Ahmed M 等人报告 RR 0.73（95% CI 0.57-0.93）。现有综述还一致提示功能状态的改善。Gera 等人的综述报告卒中 OR 0.85（95% CI 0.77-0.93；n = 85,373），而心血管和全因死亡率的发现仍不一致。主要不良心血管事件的证据有限；Gonzales-Uribe 等人的综述报告 HR 0.71（95% CI 0.60-0.86）。AMSTAR 2 将六项综述评为总体方法学可信度低，五项评为总体方法学可信度极低。CCA 为 13.2%，表明重叠度较高。所有 HR、RR 和 OR 值均为所纳入综述报告的估计值，未在本伞形综述中重新计算或定量合并。 结论：在现有证据综合层面，基于 GLP-1 的疗法在肥胖相关 HFpEF 中似乎最一致地与较少的心力衰竭住院和改善的功能容量相关。然而，综述层面的证据并未确定一致的死亡率获益，也不支持将基于 GLP-1 的疗法作为 HFpEF 的普遍改变死亡率的治疗。这些药物更宜被解释为新兴的代谢-功能疗法，其表面上的获益必须 应考虑到方法学局限性以及各综述之间存在的高度重叠。
完整摘要 · 英文原文
BACKGROUND: The cardiometabolic phenotype of obesity-related heart failure with preserved ejection fraction (HFpEF) is increasing in clinical prevalence. Existing systematic reviews and meta-analyses have primarily summarized efficacy estimates for glucagon-like peptide-1 (GLP-1)-based therapies, but the credibility and independence of these syntheses remain uncertain because methodological limitations and overlap in primary trials have not been systematically evaluated. This umbrella review therefore appraised the methodological quality, overlap, consistency, and robustness of the existing review-level evidence rather than generating another efficacy synthesis. METHODS: We conducted an umbrella review of systematic reviews, meta-analyses, and network meta-analyses evaluating GLP-1-based regimens in obesity-related HFpEF and adjacent cardiometabolic populations. PubMed, Embase, Web of Science, and the Cochrane Library were searched over the preceding decade. The systematic review or meta-analysis was the unit of analysis. Methodological quality was assessed with AMSTAR 2, and overlap of primary studies across reviews was quantified using the corrected covered area (CCA). No de novo meta-analysis was performed; primary trials were examined only to assess overlap and calculate the CCA. Review-level findings were synthesized according to effect direction, consistency, precision, sample size, methodological quality, clinical relevance, and overlap. RESULTS: Seventeen systematic reviews underwent qualitative profiling, of which 11 reported quantitative estimates relevant to the core review-level synthesis. For heart failure hospitalization, the review by Diallo et al. reported HR 0.78 (95% CI 0.73-0.84; n = 25,440). For the composite of cardiovascular death and heart failure hospitalization, Diallo et al. reported HR 0.84 (95% CI 0.78-0.89), Ahmed HM et al. reported HR 0.76 (95% CI 0.64-0.90), and Ahmed M et al. reported RR 0.73 (95% CI 0.57-0.93). Existing reviews also consistently suggested improvements in functional status. The review by Gera et al. reported OR 0.85 (95% CI 0.77-0.93; n = 85,373) for stroke, whereas findings for cardiovascular and all-cause mortality remained inconsistent. Evidence for major adverse cardiovascular events was limited; the review by Gonzales-Uribe et al. reported HR 0.71 (95% CI 0.60-0.86). AMSTAR 2 classified six reviews as having low overall methodological confidence and five as having critically low overall methodological confidence. The CCA was 13.2%, indicating high overlap. All HR, RR, and OR values were estimates reported by included reviews and were not recalculated or quantitatively combined in this umbrella review. CONCLUSIONS: At the level of existing evidence syntheses, GLP-1-based therapies appear most consistently associated with fewer heart failure hospitalizations and improved functional capacity in obesity-related HFpEF. However, the review-level evidence does not establish a consistent mortality benefit or support GLP-1-based therapy as a universal mortality-modifying treatment for HFpEF. These agents are better interpreted as emerging metabolic-functional therapies whose apparent benefits must be considered in light of methodological limitations and high overlap among reviews.