索他利嗪治療糖尿病和近期心力衰竭惡化患者可改善臨床預後
作者：
小柯機器人發布時間：2021/1/15 16:22:46
美國布列根和婦女醫院和哈佛醫學院Deepak L. Bhatt團隊研究了索他利嗪治療糖尿病和近期心力衰竭惡化患者的療效。2021年1月14日，該研究發表在《新英格蘭醫學雜誌》上。
鈉-葡萄糖共轉運蛋白2（SGLT2）抑制劑可降低穩定型心力衰竭患者因心力衰竭住院或心血管原因死亡的風險。然而，SGLT2抑制劑在失代償性心力衰竭發作後立即使用的安全性和有效性尚不清楚。
研究組進行了一項多中心、雙盲試驗，在該試驗中，招募因心力衰竭惡化而最近住院的2型糖尿病患者，將其隨機分配，分別接受索他利嗪或安慰劑治療。主要終點是心血管原因死亡和住院以及因心力衰竭而緊急就診（包括初次和後續事件）的綜合結局。
研究組共招募了1222例患者，其中索他利嗪組608例，安慰劑組614例，中位隨訪時間為9.0個月。有48.8%的患者在出院前服用首劑索他利嗪或安慰劑，51.2%在出院後2天內服用。索他利嗪組的患者中發生了245個主要終點事件，安慰劑組有255個。索他利嗪組的主要終點事件發生率為每100患者年51.0件，顯著低於安慰劑組的76.3件，風險比為0.67。
索他利嗪組心血管原因死亡率為每100患者年10.6例，安慰劑組為12.5例，風險比為0.84；索他利嗪組全因死亡率為每100患者年13.5例，安慰劑組為16.3例，風險比為0.82。索他利嗪組的腹瀉和嚴重低血糖發生率分別為6.1%和1.5%，均顯著高於安慰劑組（3.4％和0.3%）。索他利嗪組和安慰劑組中低血壓患者分別佔6.0％和4.6％，急性腎損傷患者分別佔4.1％和4.4％，差異均不顯著。在根據首次給藥時間分層的預先指定的亞組患者中，索他利嗪的臨床益處一致。
總之，對於患有糖尿病且最近心力衰竭惡化的患者，在出院前或出院後不久開始使用索他利嗪治療，與安慰劑相比，可顯著降低心血管原因死亡、住院和因心力衰竭就診的風險。
附：英文原文
Title: Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure
Author: Deepak L. Bhatt, M.D., M.P.H.,, Michael Szarek, Ph.D.,, P. Gabriel Steg, M.D.,, Christopher P. Cannon, M.D.,, Lawrence A. Leiter, M.D.,, Darren K. McGuire, M.D., M.H.Sc.,, Julia B. Lewis, M.D.,, Matthew C. Riddle, M.D.,, Adriaan A. Voors, M.D., Ph.D.,, Marco Metra, M.D.,, Lars H. Lund, M.D., Ph.D.,, Michel Komajda, M.D.,, Jeffrey M. Testani, M.D., M.T.R.,, Christopher S. Wilcox, M.D.,, Piotr Ponikowski, M.D.,, Renato D. Lopes, M.D., Ph.D.,, Subodh Verma, M.D., Ph.D.,, Pablo Lapuerta, M.D.,, and Bertram Pitt, M.D.
Issue&Volume: 2021-01-14
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.
DOI: 10.1056/NEJMoa2030183
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2030183