Sotagliflozin Cuts Risk by >50% for Heart Failure Readmission, CV Death in Phase 3 SOLOIST-WHF Trial

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In patients with type 2 diabetes (T2D) recently hospitalized for worsening heart failure (HF), treatment with sotagliflozin, a dual sodium glucose cotransporter-1 and -2 inhibitor, reduced by >50% the risk of HF readmission or a composite of cardiovascular (CV) death and HF readmission at 30 and 90 days after discharge.

The findings, from a new analysis of data from the phase 3 SOLOIST-WHF trial, were presented at the American Heart Association Scientific Sessions 2022.

Patients hospitalized for worsening symptoms of HF are at elevated risk of mortality or of readmission to the hospital, write study authors in the abstract. In fact, approximately one-quarter of HF patients will require readmission to the hospital for a HF-related event within 30 days of discharge and that percentage increases to 65% of patients who will be readmitted within 1 year, according to a statement from sotagliflozin manufacturer Lexicon Pharmaceuticals.

And so, results of the SOLOIST-WHF trial are “meaningful for the patient, the caregiver, and the healthcare system overall,” said Bertram Pitt, MD, professor of medicine emeritus at the University of Michigan, School of Medicine, and presenter of the results from the new analysis in the company statement. “Hospital readmissions are burdensome, time-consuming, and costly. This analysis provides evidence that sotagliflozin has the potential to address all of these concerns if administered to patients prior to or at hospital discharge after experiencing an episode of worsening heart failure.”

“Hospital readmissions are burdensome, time-consuming, and costly. This analysis provides evidence that sotagliflozin has the potential to address all of these concerns if administered to patients prior to or at hospital discharge after experiencing an episode of worsening heart failure.”

The multi-center, randomized, double-blinded, placebo-controlled phase 3 SOLOIST-WHF study was designed to evaluate the CV efficacy of sotagliflozin vs placebo when added to standard of care in patients with T2D who had recently been hospitalized for worsening HF.

Patients were admitted for an index event and were randomized to treatment with sotagliflozin or placebo during their hospital stay. SOLOSIT-WHF investigators evaluated the efficacy of the study drug on 30- and 90-day CV death and HF readmission (HHF or urgent visits for HF) rates after discharge.

Of 1222 randomized patients with T2D, 86% were admitted for an index WHF event. Of those, 46% (n = 563) initiated sotagliflozin treatment before or at hospital discharge. Comparisons were stratified by region and baseline left ventricular ejection fraction value (<50%, ≥50%).

FINDINGS

Within 30 days after hospital discharge, treatment with sotagliflozin showed significant relative risk reductions of >50% for readmission for non-fatal HF-related events (risk ratio (RR) 0.47, 95% CI 0.24 – 0.91; p=.023) or the composite of CV death or readmission for HF-related events (RR 0.48, 95% CI 0.27 to 0.88; p=.015). Findings at 90 days post-discharge were similar, according to the study abstract, with RR of 0.48 (95% CI 0.30 to 0.76; p=.002) for readmission for non-fatal HF-related events and RR of 0.49 (95% CI 0.32 to 0.75; p<.01) for the composite of CV death or readmission for HF-related events.

The investigators report that sotagliflozin safety during those 1- and 3-month windows was generally consistent with safety observed during the full study. Adverse events (AEs) and serious AEs were similar between the treatment and placebo groups, although an increased incidence of diarrhea and volume-related AEs was observed among participants treated with sotagliflozin. Changes in eGFR from baseline to 30 days were not appreciable, the abstract reports, but the incidence of AEs linked to acute kidney injury were lower with in the sotagliflozin-treated arm.

“The SOLOIST-WHF trial continues to yield robust findings that further help characterize and differentiate the efficacy and safety profile of sotagliflozin in patients with acute or worsening heart failure,” said Craig Granowitz, MD, PhD, Lexicon senior vice president and chief medical officer. “Importantly, based on this new analysis by Dr. Bertram Pitt, sotagliflozin may reduce the likelihood of readmission rates for heart failure events and thus reduce the significant burden on patients, caregivers and the healthcare system.”

Abstract reference: Pitt B, Bhatt, DL, Szarek J, et al. The effect of the dual SGLT1 and 2 inhibitor sotagliflozin on cardiovascular mortality and hospital readmission rates for heart failure at 30- and 90-days post discharge in patients with type 2 diabetes hospitalized for worsening heart failure in the SOLOIST-WHF trial. Abstract presented at the American Heart Association Scientific Sessions 2022; November 5-7, 2022; Chicago, IL.