Department of Internal Medicine, University of Genova, Genova, Italy.
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
J Cardiovasc Med (Hagerstown). 2023 Aug 1;24(8):537-543. doi: 10.2459/JCM.0000000000001504.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been evaluated in phase 3 randomized-controlled trials (RCTs) that enrolled individuals with heart failure and preserved ejection fraction (HFpEF) based on detailed clinical, biochemical, and echocardiographic criteria (hereafter HF-RCTs), and in cardiovascular outcomes trials (CVOTs) in diabetic patients, in which the diagnosis of HFpEF relied on medical history.
We performed a study-level meta-analysis of the efficacy of SGLT2i across different definitions of HFpEF. Three HF-RCTs (EMPEROR-Preserved, DELIVER, and SOLOIST-WHF) and four CVOTs (EMPA-REG OUTCOME, DECLARE-TIMI 58, VERTIS-CV, and SCORED) were included, for a total of 14 034 patients. SGLT2i reduced the risk of cardiovascular death or heart failure hospitalization (HFH) in all RCTs pooled together [risk ratio 0.75, 95% confidence interval (95% CI) 0.63-0.89, NNT 19], in HF-RCTs (risk ratio 0.71, 95% CI 0.52-0.97, NNT 13), and in CVOTs (risk ratio 0.78, 95% CI 0.60-0.99, NNT 26). SGLT2i also decreased the risk of HFH in all RCTs (risk ratio 0.81, 95% CI 0.73-0.90, NNT 45), in HF-RCTs (risk ratio 0.81, 95% CI 0.72-0.93, NNT 37), and in CVOTs (risk ratio 0.78, 95% CI 0.61-0.99, NNT 46). By contrast, SGLT2i were not superior to placebo for cardiovascular death or all-cause death in all RCTs, HF-RCTs, or CVOTs. Results were comparable after excluding one RCT at a time. Meta-regression analysis confirmed that the type of RCT (HF-RCT vs. CVOT) did not influence the SGLT2i effect.
In RCTs, SGLT2i improved the outcomes of patients with HFpEF regardless of how the latter was diagnosed.
钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）已在基于详细临床、生化和超声心动图标准（以下简称 HF-RCTs）纳入射血分数保留的心力衰竭（HFpEF）患者的 3 期随机对照试验（RCTs）和纳入糖尿病患者的心血管结局试验（CVOTs）中进行了评估，HFpEF 的诊断依赖于病史。
我们对不同 HFpEF 定义下 SGLT2i 的疗效进行了研究水平的荟萃分析。纳入了 3 项 HF-RCTs（EMPEROR-Preserved、DELIVER 和 SOLOIST-WHF）和 4 项 CVOTs（EMPA-REG OUTCOME、DECLARE-TIMI 58、VERTIS-CV 和 SCORED），共纳入 14034 例患者。SGLT2i 降低了所有 RCT 汇总的心血管死亡或心力衰竭住院（HFH）风险[风险比 0.75，95%置信区间（95%CI）0.63-0.89，NNH 19]，HF-RCTs 中[风险比 0.71，95%CI 0.52-0.97，NNH 13]和 CVOTs 中[风险比 0.78，95%CI 0.60-0.99，NNH 26]。SGLT2i 还降低了所有 RCTs 的 HFH 风险[风险比 0.81，95%CI 0.73-0.90，NNH 45]、HF-RCTs 中的风险[风险比 0.81，95%CI 0.72-0.93，NNH 37]和 CVOTs 中的风险[风险比 0.78，95%CI 0.61-0.99，NNH 46]。相比之下，SGLT2i 在所有 RCTs、HF-RCTs 或 CVOTs 中并未优于安慰剂用于心血管死亡或全因死亡。每次排除一项 RCT 后，结果均具有可比性。荟萃回归分析证实 RCT 类型（HF-RCT 与 CVOT）并不影响 SGLT2i 的作用。
在 RCTs 中，SGLT2i 改善了 HFpEF 患者的结局，无论后者如何诊断。
