KEY POINTS:
- Trials for those with heart failure with preserved ejection fraction have not previously demonstrated significant evidence of benefit to date
- The use of the SGLT1/2 inhibitor, sotagliflozin, results in consistent, significant benefit in those with diabetes and reduced, midrange, and preserved ejection fraction
SGLT2 inhibitors have garnered significant attention recently as medication for patients with diabetes that concurrently reduce hospital admissions in patients who have heart failure with reduced ejection fraction. Sotagliflozin, a SGLT1/2 inhibitor, is not yet approved for use in the United States but has recently been found to reduce hospitalization and death in patients with diabetes and heart failure. SCORED , a double-blind randomized controlled trial, examined risk of cardiovascular death, heart failure hospitalization, and urgent visits for heart failure in patients with type II diabetes. This trial detected a clinically significant reduction in a composite primary endpoint for those randomized to the sotagliflozin group.
SOLOIST-WHF was a second, double-blind, randomized controlled trial in patients with type II diabetes with more advanced cardiac dysfunction. Composite outcomes were similar to the SCORED trial; the study found a significant reduction in major adverse cardiac events in the sotagliflozin group when compared to placebo.
While both SCORED and SOLOIST-WHF are thought to be practice changing for those with diabetes and signs or symptoms of heart failure, little evidence-based medicine exists for those with diabetes and heart failure with preserved ejection fraction. On ACC 2021 day 3, presented as one of the highly anticipated Late Breaking Clinical Trials, Dr. Deepak L. Bhatt, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Health and Professor of Medicine at Harvard Medical School, presented pooled data from both SCORED and SOLOIST-WHF to examine cardiovascular deaths, heart failure hospitalizations, and urgent visits for heart failure in over 11,000 patients. By pooling two prior trials, Dr. Bhatt and colleagues were able to examine cardiac events in those with reduced, midrange, and preserved ejection fraction. All three subgroups (including heart failure with preserved ejection fraction) were found to have consistent, significant benefit. Substantial benefit was also found in both men and women, a significant finding given the prevalence of heart failure with preserved ejection fraction in older women.
Limitations of the trial included early cessation at the onset of the COVID-19 pandemic. Given the trial’s already positive results, it likely leads to underestimation of sotagliflozin’s benefit. The early discontinuation also resulted in the trial being underpowered for cardiovascular death (hence the presentation of on-treatment analysis, which did show a significant reduction in cardiovascular death). Lastly, some analyses were prespecified whereas others were post hoc.
Dr. Bhatt commented that “the findings are likely generalizable to SGLT2 inhibitors as a class” and that “these data should be practice changing for the medical community.” When asked what’s next in the SGLT2 trial arena, Dr. Bhatt anticipates further data coming soon for patients with heart failure with preserved ejection fraction but without diabetes from other trials, as well the examination of more endpoints from SOLOIST and SCORED, like the effect on stroke. Lastly, further analyses regarding patients with diabetes with low GFR and the effect on glycemic control of sotagliflozin will be forthcoming.