法国南锡大学CHRU Brabois医院Faiez Zannad团队研究了SGLT2抑制剂治疗射血分数降低型心力衰竭患者的疗效。2020年8月30日，该成果发表在《柳叶刀》杂志上。

两项关于达格列净和依帕列净的试验显示，钠-葡萄糖共转运蛋白2（SGLT2）抑制剂治疗伴或不伴糖尿病的射血分数降低型心力衰竭（HFrEF）患者，可有效降低心血管死亡和因心力衰竭而住院的综合风险。然而，这两项试验都不能评估心血管死亡或全因死亡的影响，也不能描述临床重要亚组的影响。

研究组对两项评估SGLT2抑制剂对伴或不伴糖尿病的HFrEF患者心血管结局影响的大型试验进行了预先指定的荟萃分析。主要终点是死亡时间。此外，研究组还评估了预先指定的亚组治疗对心血管死亡或因心力衰竭住院的综合风险的影响。

在两项试验合并的8474名患者中，经评估治疗效果使全因死亡减少了13％，心血管死亡减少了14%，差异显著。SGLT2抑制剂使心血管死亡或因心力衰竭首次住院的综合风险相对降低了26%，使因心力衰竭或心血管死亡而再次住院的综合风险降低了25%，差异显著。复合肾终点的风险也显著降低。

试验之间所有疗效的异质性均不显著。综合治疗效果显示，基于年龄、性别、糖尿病、血管紧张素受体-脑啡肽酶抑制剂(ARNI)治疗、基线肾小球滤过率（eGFR）的各亚组间疗效一致，但建议根据纽约心脏协会（NYHA）功能分类和不同种族，通过亚组相互作用进行治疗。

总之，在两个独立试验中，达格列净和依帕列净治疗对心力衰竭住院的影响是一致的，可显著改善HFrEF患者的肾功能，减少全因死亡和心血管死亡的风险。

附：英文原文

Title: SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials

Author: Faiez Zannad, Joo Pedro Ferreira, Stuart J Pocock, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Martina Brueckmann, Anne Pernille Ofstad, Egon Pfarr, Waheed Jamal, Milton Packer

Issue&Volume: 2020-08-30

Abstract: Background

Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials.

Methods

We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model.

Findings

Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77–0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76–0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68–0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68–0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43–0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race.

Interpretation

The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF.

DOI: 10.1016/S0140-6736(20)31824-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31824-9/fulltext