Post-hoc Findings From Inpefa Trial Show Benefit of Starting Drug Before Discharge

The FDA approved Inpefa (sotagliflozin) for broad heart failure treatment in late May 2023. The approval was based on results from the SCORED trial and the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-Worsening Heart Failure) trial.

Bertram Pitt, M.D., professor emeritus of the University of Michigan School of Medicine and other investigators have now completed a post hoc analysis of the SOLOIST-WHF trial. Pitt and his colleagues reported results in JAAC: Heart Failure showing that starting Inpefa before hospital discharge “markedly reduced” the risk of cardiovascular death or hospitalization for heart failure at both 30 and 90 days.

SOLOIST-WHF was a phase 3, double-blind, randomized, placebo-controlled trial that enrolled adults with type 2 diabetes who were recently admitted for worsening heart failure (WHF). Participants were assigned randomly to once-daily Inpefa at a dose of 200 mg (with a possible dose escalation to 400 mg) or placebo. Study medication was started before or within three days of discharge for the index WHF event. Cardiovascular events, including hospital readmissions for heart failure events, were documented over a nine-month (median) follow-up. The main endpoint of the post-hoc analysis was cardiovascular death or heart-failure-related event (hospitalization or urgent care visit) within 90 and 30 days after discharge for the index WHF hospitalization.

Up to 62% of patients discharged after an episode of worsening heart failure are readmitted to the hospital within one year, the researchers note. Nearly 50% are readmitted within 90 days and approximately 25% within 30 days of discharge. Mortality rates during the first 30 days after discharge can range as high as 17%. Meanwhile, the researchers noted, U.S. health care reimbursement policy penalizes hospitals with high rates of 30-day heart failure readmissions.

In the original trial (which was stopped early due to loss of funding, related to COVID-19), 290 Inpefa recipients and 306 placebo recipients started the study drug a median of seven days after admission and before discharge. Within this subgroup, 142 patients began the study drug at least one day before discharge and 454 patients on the day of discharge.

At the end of the trial, the Inpefa group had 70 events (cardiovascular deaths and heart-failure0related hospitalizations and urgent visits) versus 98 events/100 patient years in the placebo group, which was significant by day 28 of the follow-up. In the post hoc analysis of the 48.8% of participants who received the study drug before or at the time of discharge, sotagliflozin reduced the relative risk of a composite of cardiovascular mortality and HF-related hospitalizations and urgent visits by more than 40% within 90 and within 30 days of discharge. It also significantly reduced total mortality at 90 days after discharge.

Reductions in 90-day post-discharge cardiovascular mortality and heart failure events were observed across subgroups including sex, age, baseline eGFR, NT-proBNP, LVEF, and mineralocorticoid receptor agonist use. The consistent reduction in this composite endpoint in patients with HFpEF (heart failure with preserved ejection fraction) was “particularly noteworthy,” the researchers say.

Many patients admitted to the hospital with WHF have not previously received recommended therapies, and they are often discharged without or with only low doses of recommended heart failure agents.

Based on the findings from the original trial, supported by the posthoc analysis, the Pitt and colleagues advise “routinely” starting sodium glucose cotransporter treatment before discharge in patients with type 2 diabetes hospitalized for WHF.