Sotagliflozin Shows Significant Benefit for Heart Failure Across the Spectrum of Ejection Fraction

Sotagliflozin could significantly reduce the risk of cardiovascular death and worsening heart failure across the spectrum of ejection fraction, including among patients with preserved ejection fraction, according to new data from the American College of Cardiology’s 70th Annual Scientific Session (ACC.21).

While SGLT2 inhibitors dapagliflozin and empagliflozin have dominated conversation related to heart failure care in recent years, this pooled analysis of the SOLOIST and SCORED trials indicate use of the dual SGLT1/2 inhibitor sotagliflozin was associated with robust and significant reductions in worsening heart failure and cardiovascular death irrespective of baseline ejection fraction among participants.

“The benefit for patients with HFpEF is striking—this is the first trial to find a significant benefit in this population. We believe that these results merit a recommendation that patients who have both diabetes and HFpEF should be treated with sotagliflozin or another medication in its class,” said Deepak Bhatt, MD, MPH, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, in a statement.

The evolution of SGLT2 inhibitors from oral agents with a modest effect on glycemic levels to a heart failure and chronic kidney disease treatment has taken cardiology by storm in the last half decade. At AHA 2020, a new name was brought into the mix when the SCORED and SOLOIST trials demonstrated the safety and efficacy of sotagliflozin in patients with diabetes and comorbid heart failure or chronic kidney disease.

For the current analysis, investigators from the trials pooled data from both trials and sought to determine the effectiveness of sotagliflozin according to ejection fraction at study entry. With only 22 patients from the trials missing this information, investigators had a cohort of 11,784 patients for inclusion in their study. Of these, 4500 had a history of heart failure.

Initial analysis of data from the entire cohort indicated sotagliflozin was associated with a significant reduction in the primary composite outcome across the spectrum of ejection fraction. Specific hazard ratios for each group were 0.78 (95% CI, 0.63-0.96; P=.02) for ejection fraction less than 40%, 0.61 (95% CI,0.44-0.84; P=.003) for ejection fraction of 40 to less than 50%, 0.70 (95% CI, 0.57-0.86; P=.0008) for those with an ejection fraction equal to or greater than 50% (P for interaction with EF=.46; P for interaction with continuous EF=.49).

Similar results were seen among the subgroup of patients with a history of heart failure. Specific hazard ratios for each group were 0.78 (95% CI, 0.63-0.96; P=.02) for an ejection fraction less than 40%, 0.57 (95% CI, 0.40-0.82; P=.002) for those with an ejection fraction of 40-50%, 0.67 (95% CI, 0.51-0.89; P=.006) for an ejection fraction greater than 50% (P for interaction with EF category=0.35; P for interaction with continuous EF=0.33).

“We saw a significant reduction in the primary endpoint irrespective of patients’ ejection fraction at study entry,” Bhatt said. “The magnitude of the benefit in patients with HFpEF was surprising. Sotagliflozin offers a meaningful, incremental advance in improving outcomes for this challenging group of patients.”

For a greater understanding of the study’s results and how they inform clinicians on the effects of sotagliflozin, Practical Cardiology reached out to Bhatt for his perspective and insight as principal investigator of the SOLOIST and SCORED trials.

This study, “ Benefits of Sodium Glucose Co-transporter-1/2 Inhibition with Sotagliflozin Across the Full Spectrum of Ejection Fraction, Including Heart Failure with Preserved Ejection Fraction,” was presented at ACC.21