SGLT2 抑制剂用于 2 型糖尿病的心血管和肾脏结局的一级和二级预防：心血管结局试验的系统评价和荟萃分析。

SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

机构信息

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.

出版信息

Lancet. 2019 Jan 5;393(10166):31-39. doi: 10.1016/S0140-6736(18)32590-X. Epub 2018 Nov 10.

DOI:10.1016/S0140-6736(18)32590-X

PMID:30424892

Abstract

BACKGROUND

The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined.

METHODS

We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function.

FINDINGS

We included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83-0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80-0·93]) and not in those without (1·00 [0·87-1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48-0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline.

INTERPRETATION

SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure.

FUNDING

None.

摘要

背景

钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）对特定心血管和肾脏结局的影响程度，以及这种异质性是否基于关键的基线特征，目前仍不清楚。

方法

我们对 SGLT2i 治疗 2 型糖尿病患者的心血管结局的随机、安慰剂对照临床试验进行了系统评价和荟萃分析。我们在 PubMed 和 Embase 上检索了截至 2018 年 9 月 24 日发表的试验。使用标准化数据表格完成数据检索和提取，任何分歧均通过共识解决。疗效终点包括主要不良心血管事件（心肌梗死、卒中和心血管死亡）、心血管死亡或心力衰竭住院的复合终点以及肾脏疾病进展。试验间汇总了风险比（HR）及其 95%置信区间（CI），并根据基线时是否存在动脉粥样硬化性心血管疾病、心力衰竭以及肾功能程度对疗效终点进行分层。

结果

我们纳入了 3 项已确定试验的数据，共涉及 34322 名患者（60.2%患有已确立的动脉粥样硬化性心血管疾病），其中有 3342 例主要不良心血管事件、2028 例心血管死亡或心力衰竭住院事件以及 766 例肾脏复合结局。SGLT2i 使主要不良心血管事件减少了 11%（HR 0.89 [95%CI 0.83-0.96]，p=0.0014），但这种获益仅见于有动脉粥样硬化性心血管疾病的患者（0.86 [0.80-0.93]），而在无动脉粥样硬化性心血管疾病的患者中并未见到（1.00 [0.87-1.16]，p 交互=0.0501）。SGLT2i 使心血管死亡或心力衰竭住院的风险降低了 23%（0.77 [0.71-0.84]，p<0.0001），在有和无动脉粥样硬化性心血管疾病以及有和无心力衰竭病史的患者中均观察到了相似的获益。SGLT2i 使肾脏疾病进展的风险降低了 45%（0.55 [0.48-0.64]，p<0.0001），在有和无动脉粥样硬化性心血管疾病的患者中均观察到了相似的获益。SGLT2i 的获益程度与基线肾功能相关，在基线肾功能更差的患者中，心力衰竭住院的减少幅度更大（p 交互=0.0073），而肾脏疾病进展的减少幅度更小（p 交互=0.0258）。