心力衰竭、外周动脉疾病和达格列净：DAPA-HF 和 DELIVER 的患者水平荟萃分析。
Heart failure, peripheral artery disease, and dapagliflozin: a patient-level meta-analysis of DAPA-HF and DELIVER.
机构信息
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
出版信息
Eur Heart J. 2023 Jun 25;44(24):2170-2183. doi: 10.1093/eurheartj/ehad276.
AIMS
Because an increased risk of amputation with canagliflozin was reported in the CANVAS trials, there has been a concern about the safety of sodium-glucose cotransporter 2 inhibitors in patients with peripheral artery disease (PAD) who are at higher risk of amputation.
METHODS AND RESULTS
A patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the efficacy and safety of dapagliflozin in patients with heart failure (HF) with reduced, mildly reduced/preserved ejection fraction, respectively, was conducted. In both trials, the primary outcome was the composite of worsening HF or cardiovascular death, and amputation was a prespecified safety outcome. Peripheral artery disease history was available for 11 005 of the total 11 007 patients. Peripheral artery disease was reported in 809 of the 11 005 patients (7.4%). Median follow-up was 22 months (interquartile range 17-30). The rate of the primary outcome (per 100 person-years) was higher in PAD patients than that in non-PAD patients: 15.1 [95% confidence interval (CI) 13.1-17.3) vs. 10.6 (10.2-11.1]; adjusted hazard ratio 1.23 (95% CI 1.06-1.43). The benefit of dapagliflozin on the primary outcome was consistent in patients with [hazard ratio 0.71 (95% CI 0.54-0.94)] and without PAD [0.80 (95% CI 0.73-0.88)] (Pinteraction = 0.39). Amputations, while more frequent in PAD patients, were not more common with dapagliflozin, compared with placebo, irrespective of PAD status (PAD, placebo 4.2% vs. dapagliflozin 3.7%; no PAD, placebo 0.4% vs. dapagliflozin 0.4%) (Pinteraction = 1.00). Infection rather than ischaemia was the main trigger for amputation, even in patients with PAD.
CONCLUSION
The risk of worsening HF or cardiovascular death was higher in patients with PAD, as was the risk of amputation. The benefits of dapagliflozin were consistent in patients with and without PAD, and dapagliflozin did not increase the risk of amputation.
目的
由于在 CANVAS 试验中报告了卡格列净会增加截肢风险，因此人们一直担心钠-葡萄糖共转运蛋白 2 抑制剂在有更高截肢风险的外周动脉疾病（PAD）患者中的安全性。
方法和结果
对 DAPA-HF 和 DELIVER 试验进行了患者水平的汇总分析，这两项试验分别评估了达格列净在射血分数降低、轻度降低/保留的心衰患者中的疗效和安全性。在这两项试验中，主要终点是心衰恶化或心血管死亡的复合终点，截肢是预先规定的安全性终点。总共 11007 例患者中有 11005 例患者有外周动脉疾病史。在这 11005 例患者中，809 例（7.4%）报告有外周动脉疾病。中位随访时间为 22 个月（四分位距 17-30）。PAD 患者的主要终点（每 100 人年发生率）高于非 PAD 患者：15.1[95%置信区间（CI）13.1-17.3] vs. 10.6[10.2-11.1]；调整后的风险比为 1.23（95%CI 1.06-1.43）。在有 PAD（风险比 0.71[95%CI 0.54-0.94]）和无 PAD（0.80[95%CI 0.73-0.88]）的患者中，达格列净对主要终点的获益是一致的（P 交互=0.39）。与安慰剂相比，尽管 PAD 患者的截肢更常见，但达格列净并未增加截肢的风险（PAD，安慰剂 4.2% vs. 达格列净 3.7%；无 PAD，安慰剂 0.4% vs. 达格列净 0.4%）（P 交互=1.00）。感染而不是缺血是截肢的主要触发因素，即使在外周动脉疾病患者中也是如此。
结论
PAD 患者的恶化 HF 或心血管死亡风险更高，截肢风险也更高。达格列净在有和无 PAD 的患者中的获益是一致的，并且达格列净不会增加截肢的风险。
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