Findings from the SOLOIST-WHF trial demonstrated that sotagliflozin can lead to reduced cardiovascular-related deaths, hospitalizations, and urgent visits due to heart failure in patients with diabetes and recent worsening heart failure.
A team led by Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart and Vascular Center, evaluated the safety and efficacy of the sodium–glucose cotransporter 2 (SGLT2) inhibitor initiated in such patients before or shortly after discharge.
“The safety and potential efficacy of initiating SGLT2 inhibition soon after an episode of decompensated heart failure remain uncertain,” they wrote.
“Potential safety concerns include the risks of hypotension and precipitation of kidney failure among patients with fluctuating volume status and renal function who are receiving treatment with other drugs that might also affect the glomerular filtration rate (GFR).”
The Study: Design and Methodology
In their multicenter, double-blind trial, the team randomly assigned patients 1:1 to receive either sotagliflozin or placebo.
Thus, the primary endpoint was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure.
All eligible participants were between 18-85 years of age and had been hospitalized due to the presence of symptoms related to heart failure. All patients had a previous diagnosis of type 2 diabetes before index admission or were diagnosed with type 2 diabetes at index admission.
Patients with end-stage heart failure or recent acute coronary syndrome, stroke, percutaneous coronary intervention or coronary-artery bypass surgery, or an estimated GFR of less than 30 ml per minute per 1.73 m2 of body-surface area were excluded from study.
During the trial, all enrolled patients (n = 1222) received 200 mg of sotagliflozin or placebo once daily, in addition to a dose increase to 400 mg (provided there were no major side effects).
The investigators noted that the 1st dose of either treatment was administered before discharge in 48.8% of patients, and the 2nd dose was administered a median of 2 days following discharge in the remainder of patients.
Follow-up visits were scheduled at weeks 1, 2, and 4, at month 4, and then every 4 months. Patients were followed for a median of 9 months.
Bhatt and colleagues reported that primary endpoint events occurred in 600 patients—245 in the sotagliflozin group and 355 in the placebo group.
Furthermore, the rate of primary endpoint events—defined as the number of events per 100 patient-years—was notably lower in the sotagliflozin group than in the placebo (51.0 vs. 76.3, respectively; hazard ratio [HR], 0.67; 95% CI, 0.52-0.85; P<0.001).
In the cohort that received sotagliflozin, the rate of death from cardiovascular causes was 10.6 —compared with 12.5 in the placebo cohort (HR, 0.84; 95% CI, 0.58-1.22).
The rate of death from any cause was 13.5 for sotaglifozin and 16.3 for placebo (HR, 0.82; 95% CI, 0.59-1.14).
As for adverse events, diarrhea was more common with sotagliflozin (6.1%) than with placebo (3.4%). This same trend was noted for severe hypoglycemia (sotagliflozin, 1.5% vs placebo, 0.3%).
However, the percentage of patients in both cohorts was similar in regard to hypotension (sotagliflozin, 6.0% vs placebo, 4.6%) and acute kidney injury (sotagliflozin, 4.1% and placebo, 4.4%).
Conclusion and Perspective
Despite these encouraging findings, the team acknowledged various limitations, including the early discontinuation of the trial due to loss of funding.
“Although the trial suggested that there was a beneficial effect with respect to the original primary end point of the first occurrence of either death from cardiovascular causes or hospitalization for heart failure, the earlier-than-planned closure of the trial limited the statistical power to assess the secondary end points, such as death from cardiovascular causes,” Bhatt and colleagues wrote.
Nonetheless, they indicated the evidence accumulated during the study suggests promise of SGLT2 initiation before or immediately following discharge in patients with worsening heart failure.
“Early initiation of therapy represents an important opportunity to improve outcomes, as indicated by the high rate of primary end-point events at 90 days after randomization among the patients receiving placebo,” they wrote.
The study, “Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure,” was published online in The New England Journal of Medicine.