SGLT2抑制劑治療射血分數降低型心力衰竭患者療效顯著

SGLT2抑制劑治療射血分數降低型心力衰竭患者療效顯著

作者：

小柯機器人

發布時間：2020/9/1 20:09:55

法國南錫大學CHRU Brabois醫院Faiez Zannad團隊研究了SGLT2抑制劑治療射血分數降低型心力衰竭患者的療效。2020年8月30日，該成果發表在《柳葉刀》雜誌上。

兩項關於達格列淨和依帕列淨的試驗顯示，鈉-葡萄糖共轉運蛋白2（SGLT2）抑制劑治療伴或不伴糖尿病的射血分數降低型心力衰竭（HFrEF）患者，可有效降低心血管死亡和因心力衰竭而住院的綜合風險。然而，這兩項試驗都不能評估心血管死亡或全因死亡的影響，也不能描述臨床重要亞組的影響。

研究組對兩項評估SGLT2抑制劑對伴或不伴糖尿病的HFrEF患者心血管結局影響的大型試驗進行了預先指定的薈萃分析。主要終點是死亡時間。此外，研究組還評估了預先指定的亞組治療對心血管死亡或因心力衰竭住院的綜合風險的影響。

在兩項試驗合併的8474名患者中，經評估治療效果使全因死亡減少了13％，心血管死亡減少了14%，差異顯著。SGLT2抑制劑使心血管死亡或因心力衰竭首次住院的綜合風險相對降低了26%，使因心力衰竭或心血管死亡而再次住院的綜合風險降低了25%，差異顯著。複合腎終點的風險也顯著降低。

試驗之間所有療效的異質性均不顯著。綜合治療效果顯示，基於年齡、性別、糖尿病、血管緊張素受體-腦啡肽酶抑制劑(ARNI)治療、基線腎小球濾過率（eGFR）的各亞組間療效一致，但建議根據紐約心臟協會（NYHA）功能分類和不同種族，通過亞組相互作用進行治療。

總之，在兩個獨立試驗中，達格列淨和依帕列淨治療對心力衰竭住院的影響是一致的，可顯著改善HFrEF患者的腎功能，減少全因死亡和心血管死亡的風險。

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