Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial.

Szarek, Michael; Bhatt, Deepak L; Steg, Ph Gabriel; Cannon, Christopher P; Leiter, Lawrence A; McGuire, Darren K; Lewis, Julia B; Riddle, Matthew C; Voors, Adriaan A; Metra, Marco; Lund, Lars H; Komajda, Michel; Testani, Jeffrey M; Wilcox, Christopher S; Ponikowski, Piotr; Lopes, Renato D; Banks, Phillip; Tesfaye, Eshetu; Ezekowitz, Justin A; Verma, Subodh; Pitt, Bertram

BACKGROUND In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%. OBJECTIVE To determine whether sotagliflozin increased the prespecified efficacy outcome of days alive and out of the hospital (DAOH) in the SOLOIST-WHF trial. DESIGN Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT03521934). SETTING 306 sites in 32 countries. PARTICIPANTS 1222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure. INTERVENTION 200 mg of sotagliflozin once daily (with a possible dose increase to 400 mg) or matching placebo. MEASUREMENTS The primary analysis included hospitalizations for any reason on the basis of investigator-reported incidence and duration of admissions after randomization. Days alive and out of the hospital and its converse (days dead and days in the hospital) were analyzed using prespecified Poisson regression models. RESULTS Although similar proportions of patients in the sotagliflozin and placebo groups were hospitalized at least once (38.5% vs. 41.4%), fewer patients in the sotagliflozin group were hospitalized more than once (16.3% vs. 22.1%). There were 64 and 76 deaths in the sotagliflozin and placebo groups, respectively. The DAOH rate in the sotagliflozin group was 3% higher than in the placebo group (rate ratio [RR], 1.03 [95% CI, 1.00 to 1.06]; P = 0.027). This difference was primarily driven by a reduction in the rate of days dead (RR, 0.71 [CI, 0.52 to 0.99]; P = 0.041) rather than by a reduction in the rate of days hospitalized for any cause. For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital for 3% or 2.9 more days than those in the placebo group (91.8 vs. 88.9 days); this difference reflected a 2.6-day difference in days dead (6.3 vs. 8.9 days) and a 0.3-day difference in days in the hospital (1.9 vs. 2.2 days). LIMITATION Other than heart failure, the primary reason for each hospitalization was unspecified. CONCLUSION Sotagliflozin increased DAOH, a metric that may provide an additional patient-centered outcome to capture the totality of disease burden. Future studies are needed to quantify the consequences of increasing DAOH in terms of health economics and patient quality of life. PRIMARY FUNDING SOURCE Sanofi at initiation and Lexicon Pharmaceuticals at completion.