Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, USA,
Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, USA.
Cardiorenal Med. 2020;10(1):1-10. doi: 10.1159/000503919. Epub 2019 Nov 19.
Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease (ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m2 in particular.
We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model.
The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87-0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77-1.02) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for all-cause mortality was 0.9 (0.84-0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81-0.99) in the general population and 0.82 (0.62-1.07) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for heart failure hospitalizations was 0.71 (0.63-0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56-0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m2 0.67 (0.59-0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76-0.84).
SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m2. SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m2.
先前的荟萃分析表明，钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）主要对已患有动脉粥样硬化性心血管疾病（ASCVD）的患者有益，但对 ASCVD 风险患者的疗效尚不确定。此外，在估计肾小球滤过率（eGFR）<60mL/min/1.73m2 的患者中，CV 结局试验中 SGLT2i 有益的心脏肾脏结局证据仍不明确。坎格列净是 SGLT2i 之一，最近在一项针对患有慢性肾脏病的糖尿病患者的大型随机对照试验中进行了研究。因此，有必要了解作为一个整体针对 SGLT2i 治疗的人群的综合结局，无论其 ASCVD 状况如何。因此，本荟萃分析将评估 SGLT2i 在心血管和肾脏结局方面的疗效，包括一般人群和 eGFR<60mL/min/1.73m2 的患者。
我们在 PubMed 和 Cochrane 数据库中搜索了涉及 SGLT2i 的随机、安慰剂对照研究。我们检查了心血管死亡、非致死性心肌梗死、非致死性卒中和心力衰竭住院的复合心血管结局。还分析了肾脏复合结局和蛋白尿进展。使用固定效应模型计算了汇总相对风险（RR）及其 95%置信区间（CI）。
搜索共产生了 252 篇文章。在排除其他不相关的研究后，最终有 4 项研究纳入荟萃分析。在一般研究人群中，复合心血管结局的汇总 RR（95%CI）为 0.93（0.87-0.99），需要治疗的人数（NNT）为 167，在 eGFR<60mL/min/1.73m2 的患者中为 0.89（0.77-1.02）。全因死亡率的汇总 RR 为 0.9（0.84-0.97），NNT=143。一般人群中单纯心血管原因死亡的汇总 RR 为 0.89（0.81-0.99），eGFR<60mL/min/1.73m2 的患者为 0.82（0.62-1.07）。心力衰竭住院的汇总 RR 为 0.71（0.63-0.79），NNT=91。关于肾脏结局，复合肾脏结局的汇总 RR 为 0.63（0.56-0.71），NNT=67；即使在 eGFR<60mL/min/1.73m2 的患者中也是如此，为 0.67（0.59-0.76）。最后，蛋白尿进展的汇总 RR 为 0.80（0.76-0.84）。
SGLT2i 与显著降低的主要不良心血管事件、心力衰竭住院和全因死亡率相关。证据在降低心力衰竭住院率方面最强。然而，在 eGFR<60mL/min/1.73m2 的亚组人群中，证据较弱。SGLT2i 还与显著降低的不良肾脏事件相关，即使在 eGFR<60mL/min/1.73m2 的人群中也有这些效果。
