Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.Methods: This was a collaborative trial-level meta-analysis from the SGLT2i meta-analysis cardio-renal trialists consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across three patient populations (diabetes at high risk for atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], or chronic kidney disease [CKD]). The outcomes of interest were MACE (composite of CV death, myocardial infarction [MI], or stroke), individual components of MACE (inclusive of fatal and non-fatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i vs. placebo were meta-analyzed across trials and examined across key subgroups (established ASCVD, prior MI, diabetes, prior HF, albuminuria, CKD stages and risk groups).Results: A total of 78,607 patients across 11 trials were included: 42,568 (54.2%), 20,725 (26.4%), and 15,314 (19.5%) were included from trials of patients with diabetes at high risk for ASCVD, HF, or CKD, respectively. SGLT2i reduced the rate of MACE by 9% (HR 0.91 [95% CI 0.87-0.96], p<0.0001) with a consistent effect across all three patient populations (I²=0%) and across all key subgroups. This effect was primarily driven by a reduction in CV death (HR 0.86 [0.81-0.92], p<0.0001), with no significant effect for MI in the overall population (HR 0.95 [0.87-1.04], p=0.29), and no effect on stroke (HR 0.99 [0.91-1.07], p=0.77). The benefit for CV death was driven primarily by reductions in HF death and sudden cardiac death (HR 0.68 [0.46-1.02] and HR 0.86 [0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (P_int=0.02).Conclusions: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of ASCVD, diabetes, kidney function or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of CV death, particularly HF and sudden cardiac death, without a significant effect on MI in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.

中文翻译：

---

钠葡萄糖协同转运蛋白 2 抑制剂和主要不良心血管结局：SMART-C 协作荟萃分析

背景：钠葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 持续改善心力衰竭和肾脏相关结局；然而，对不同患者群体的主要不良心血管事件 (MACE) 的影响尚不清楚。 方法：这是 SGLT2i 荟萃分析心肾试验者联盟的协作试验级荟萃分析，其中包括所有 3 期安慰剂SGLT2i 在三个患者群体（患有动脉粥样硬化性心血管疾病 [ASCVD]、心力衰竭 [HF] 或慢性肾病 [CKD] 高风险的糖尿病）中进行的对照、结果试验。感兴趣的结果是 MACE（心血管死亡、心肌梗塞 [MI] 或中风的综合）、MACE 的各个组成部分（包括致命和非致命事件）、全因死亡率和死亡亚型。对 SGLT2i 与安慰剂的效果估计进行了跨试验的荟萃分析，并在关键亚组（已确诊的 ASCVD、既往 MI、糖尿病、既往 HF、白蛋白尿、CKD 分期和风险组）中进行了检查。 结果：11 项试验中总共有 78,607 名患者接受了治疗。包括：分别纳入了 42,568 名 (54.2%)、20,725 名 (26.4%) 和 15,314 名 (19.5%) 患有 ASCVD、HF 或 CKD 高风险糖尿病患者的试验。 SGLT2i 将 MACE 发生率降低了 9%（HR 0.91 [95% CI 0.87-0.96]，p<0.0001），在所有三个患者群体（I ² = 0%）和所有关键亚组中具有一致的效果。这种效应主要是由于心血管死亡的减少所致（HR 0.86 [0.81-0.92]，p<0.0001），而对总体人群中的 MI 没有显着影响（HR 0.95 [0.87-1.04]，p=0.29），并且对中风没有影响（HR 0.99 [0.91-1.07]，p=0.77）。心血管死亡的获益主要是由于心力衰竭死亡和心源性猝死的减少（HR 分别为 0.68 [0.46-1.02] 和 HR 0.86 [0.78-0.95]），并且在各个亚组之间基本一致，可能的例外是更多在蛋白尿患者中尤为明显（P _int =0.02）。结论：SGLT2i 降低了广泛患者的 MACE 风险，无论基线时 ASCVD、糖尿病、肾功能或其他主要临床特征如何。这种效应主要是由于心血管死亡（尤其是心力衰竭和心源性猝死）的减少而产生的，但对总体人群中的心肌梗死没有显着影响，对中风也没有影响。这些数据可能有助于为心血管-肾脏-代谢疾病范围内的 SGLT2i 疗法的选择提供信息。