索格列净治疗伴有近期恶化心力衰竭的糖尿病患者。

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.

机构信息

From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); State University of New York Downstate School of Public Health, Brooklyn (M.S.); Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148 (P.G.S.), and Paris Sorbonne University and Groupe Hospitalier Paris Saint Joseph (M.K.), Paris; Li Ka Shing Knowledge Institute (L.A.L., S.V.) and the Divisions of Endocrinology and Metabolism (L.A.L.) and Cardiac Surgery (S.V.), St. Michael's Hospital, and the Departments of Medicine and Nutritional Sciences (L.A.L) and Surgery and Pharmacology and Toxicology (S.V.), University of Toronto, Toronto; University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) - both in Texas; Vanderbilt University, Nashville (J.B.L.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); University of Groningen-University Medical Center Groningen, Groningen, the Netherlands (A.A.V); Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy (M.M.); Karolinska Institutet, Stockholm (L.H.L.); Yale University, New Haven, CT (J.M.T.); Georgetown University, Washington, DC (C.S.W.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and the University of Michigan, Ann Arbor (B.P.).

出版信息

N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16.

DOI:10.1056/NEJMoa2030183

PMID:33200892

Abstract

BACKGROUND

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown.

METHODS

We performed a multicenter, double-blind trial in which patients with type 2 diabetes mellitus who were recently hospitalized for worsening heart failure were randomly assigned to receive sotagliflozin or placebo. The primary end point was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent events). The trial ended early because of loss of funding from the sponsor.

RESULTS

A total of 1222 patients underwent randomization (608 to the sotagliflozin group and 614 to the placebo group) and were followed for a median of 9.0 months; the first dose of sotagliflozin or placebo was administered before discharge in 48.8% and a median of 2 days after discharge in 51.2%. Among these patients, 600 primary end-point events occurred (245 in the sotagliflozin group and 355 in the placebo group). The rate (the number of events per 100 patient-years) of primary end-point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). The rate of death from cardiovascular causes was 10.6 in the sotagliflozin group and 12.5 in the placebo group (hazard ratio, 0.84; 95% CI, 0.58 to 1.22); the rate of death from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (hazard ratio, 0.82; 95% CI, 0.59 to 1.14). Diarrhea was more common with sotagliflozin than with placebo (6.1% vs. 3.4%), as was severe hypoglycemia (1.5% vs. 0.3%). The percentage of patients with hypotension was similar in the sotagliflozin group and the placebo group (6.0% and 4.6%, respectively), as was the percentage with acute kidney injury (4.1% and 4.4%, respectively). The benefits of sotagliflozin were consistent in the prespecified subgroups of patients stratified according to the timing of the first dose.

CONCLUSIONS

In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo. (Funded by Sanofi and Lexicon Pharmaceuticals; SOLOIST-WHF ClinicalTrials.gov number, NCT03521934.).

摘要

背景

钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可降低稳定心力衰竭患者因心血管原因住院或心力衰竭死亡的风险。然而，在心力衰竭失代偿发作后不久开始使用 SGLT2 抑制剂的安全性和有效性尚不清楚。

方法

我们进行了一项多中心、双盲试验，其中最近因心力衰竭恶化住院的 2 型糖尿病患者被随机分配接受索格列净或安慰剂治疗。主要终点是心血管原因死亡和心力衰竭住院和紧急就诊的总次数（首次和随后的事件）。由于赞助商资金损失，试验提前结束。

结果

共有 1222 名患者接受了随机分组（索格列净组 608 例，安慰剂组 614 例），中位随访时间为 9.0 个月；在 48.8%的患者中，首次给予索格列净或安慰剂的时间为出院前，在 51.2%的患者中为出院后中位数 2 天。在这些患者中，有 600 例发生主要终点事件（索格列净组 245 例，安慰剂组 355 例）。索格列净组的主要终点事件发生率（每 100 患者年发生的事件数）低于安慰剂组（51.0 比 76.3；风险比，0.67；95%置信区间 [CI]，0.52 至 0.85；P<0.001）。索格列净组心血管原因死亡的发生率为 10.6%，安慰剂组为 12.5%（风险比，0.84；95%CI，0.58 至 1.22）；任何原因导致的死亡率，索格列净组为 13.5%，安慰剂组为 16.3%（风险比，0.82；95%CI，0.59 至 1.14）。索格列净组腹泻的发生率高于安慰剂组（6.1%比 3.4%），严重低血糖的发生率也高于安慰剂组（1.5%比 0.3%）。索格列净组低血压的发生率与安慰剂组相似（分别为 6.0%和 4.6%），急性肾损伤的发生率也相似（分别为 4.1%和 4.4%）。根据首次剂量的时间预先指定的患者亚组中，索格列净的益处是一致的。