Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial.

• Tác giả: Rahul Aggarwal, Phillip Banks, Deepak L Bhatt, Christopher P Cannon, Amy K Carroll, David Z I Cherney, Michael J Davies, Silvio E Inzucchi, Mikhail N Kosiborod, Lawrence A Leiter, Julia B Lewis, Renato D Lopes, R Preston Mason, Darren K McGuire, Bertram Pitt, Kausik K Ray, Matthew C Riddle, Benjamin M Scirica, Ph Gabriel Steg, Michael Szarek, Jacob A Udell, Subodh Verma
• Ngôn ngữ: eng
• Ký hiệu phân loại: 940.454 Events of 1914
• Thông tin xuất bản: England : The lancet. Diabetes & endocrinology , 2025
• Bộ sưu tập: NCBI
• ID: 181899

Tóm tắt

 BACKGROUND: Sodium-glucose co-transporter (SGLT)-2 inhibitors have shown consistent benefit in improving heart failure-related outcomes but not ischaemic cardiovascular events such as myocardial infarction or stroke. We assessed if the dual SGLT1/2 inhibitor sotagliflozin improves ischaemic outcomes. METHODS: We did a prespecified secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomised clinical trial enrolling patients (aged ≥18 years) with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min per 1·73 m FINDINGS: 10 584 patients were enrolled and randomly assigned to sotagliflozin (n=5292 [50·0%]) or placebo (n=5292 [50·0%]) between Dec 8, 2017 and Jan 20, 2020 (median age 69 years [IQR 63-74]
  4754 [44·9%] female patients and 5830 [55·1%] male patients). 5144 (48·6%) patients had a history of cardiovascular disease, of whom 2108 (19·9% of the total population) had a history of myocardial infarction, 946 (8·9%) had a history of stroke, and 2375 (22·4%) had a history of coronary revascularisation. Patients in the sotagliflozin group had a significantly lower rate of total MACE than those in the placebo group (4·8 events per 100 person-years vs 6·3 events per 100 person-years
  hazard ratio [HR] 0·77 [95% CI 0·65-0·91]
  p=0·0020). Interaction analyses suggested a consistent effect of sotagliflozin on total MACE among stratified subgroups without evidence of heterogeneity. Additionally, sotagliflozin significantly reduced the rate of myocardial infarction (1·8 events per 100 person-years vs 2·7 events per 100 person-years
  HR 0·68 [0·52-0·89]
  p=0·0041) and stroke (1·2 events per 100 person-years vs 1·8 events per 100 person-years
  HR 0·66 [0·48-0·91]
  p=0·012) compared with placebo. INTERPRETATION: Sotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk. The ischaemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism. FUNDING: Lexicon Pharmaceuticals.