Philip Mevin A, Webb Carolyn M, Chakraborty Turja, Collins Peter
National Heart and Lung Institute, Imperial College London, London, UK.
Royal Brompton Hospital, London, UK.
ESC Heart Fail. 2024 Dec;11(6):3539-3550. doi: 10.1002/ehf2.14979. Epub 2024 Jul 23.
Recent evidence suggests that medications not primarily targeting the cardiovascular (CV) system may have cardioprotective effects in patients with heart failure (HF), in particular the anti-diabetic therapies sodium-glucose co-transporter-2 (SGLT-2) antagonists and glucagon-like peptide-1 (GLP-1) agonists. We conducted a systematic review to assess the pooled evidence for the use of SGLT-2 antagonists and GLP-1 agonists in patients with HF and the effect of biological sex on the results.
MEDLINE, Embase, Cochrane Library and clinical trial databases were searched until February 2023. Randomized controlled trials (RCTs) published in English that included adult participants with HF who were randomized to an SGLT-2 antagonist or GLP-1 agonist with a primary or secondary outcome of HF hospitalization (HFH) or CV death were eligible for inclusion. Data pooling was undertaken using a random effects model and odds ratios (ORs) to determine the association between drug and outcome. Sub-group analyses to investigate sex differences were conducted.
Six RCTs were included (24 781 patients). Four studies investigated SGLT-2 antagonists, and two studies examined GLP-1 agonists. SGLT-2 antagonists improved HFH {OR [95% confidence interval (CI)]: 0.69 [0.63, 0.77], P < 0.001} and CV death [0.87 (0.78, 0.97), P = 0.01] independent of diabetes status, with excellent homogeneity across all four studies. No beneficial effects were found for GLP-1 agonists. The effects of SGLT-2 antagonists on HFH and CV death were similar in men and women [OR (95% CI): HFH, 0.70 (0.64, 0.76), P < 0.001 and 0.58 (0.46, 0.74), P < 0.001, respectively; CV death, 0.86 (0.78, 0.95), P = 0.003 and 0.84 (0.73, 0.96), P = 0.01, respectively], and the neutral effect of GLP-1 agonists on HFH and CV death was similar in men and women (all P > 0.05).
SGLT-2 antagonists but not GLP-1 agonists beneficially affect HFH and CV death in patients with HF with or without diabetes. We show for the first time that GLP-1 agonists have a neutral effect on HFH and CV death in both male and female HF patients and a reduction in HFH and CV death in male and female HF patients taking SGLT-2 antagonists.
最近有证据表明，并非主要针对心血管（CV）系统的药物可能对心力衰竭（HF）患者具有心脏保护作用，尤其是抗糖尿病疗法钠-葡萄糖协同转运蛋白2（SGLT-2）拮抗剂和胰高血糖素样肽1（GLP-1）激动剂。我们进行了一项系统评价，以评估在HF患者中使用SGLT-2拮抗剂和GLP-1激动剂的汇总证据以及生物学性别对结果的影响。
检索MEDLINE、Embase、Cochrane图书馆和临床试验数据库直至2023年2月。以英文发表的随机对照试验（RCT），纳入成年HF患者，这些患者被随机分配至SGLT-2拮抗剂或GLP-1激动剂组，主要或次要结局为HF住院（HFH）或CV死亡，符合纳入标准。采用随机效应模型和比值比（OR）进行数据合并，以确定药物与结局之间的关联。进行亚组分析以研究性别差异。
纳入6项RCT（24781例患者）。4项研究调查了SGLT-2拮抗剂，2项研究考察了GLP-1激动剂。SGLT-2拮抗剂可改善HFH{OR[95%置信区间（CI）]：0.69[0.63，0.77]，P<0.001}和CV死亡[0.87（0.78，0.97），P=0.01]，与糖尿病状态无关，所有4项研究的同质性良好。未发现GLP-1激动剂有有益作用。SGLT-2拮抗剂对HFH和CV死亡的影响在男性和女性中相似[OR（95%CI）：HFH分别为0.70（0.64，0.76），P<0.001和0.58（0.46，0.74），P<0.001；CV死亡分别为0.86（0.78，[0.95），P=0.003和0.84（0.73，0.96），P=0.01]，GLP-1激动剂对HFH和CV死亡的中性作用在男性和女性中相似（所有P>0.05）。
SGLT-2拮抗剂而非GLP-1激动剂对有或无糖尿病的HF患者的HFH和CV死亡有有益影响。我们首次表明，GLP-1激动剂对男性和女性HF患者的HFH和CV死亡具有中性作用，而服用SGLT-2拮抗剂的男性和女性HF患者的HFH和CV死亡有所减少。
