Pre-/post-discharge sotagliflozin may reduce CV death, hospitalization in T2D patients with HF

Sotagliflozin given pre- or shortly post-discharge to patients with type 2 diabetes (T2D) recently hospitalized for worsening heart failure (HF) may result in a reduced risk of cardiovascular (CV) death, hospitalization, or urgent visits for HF, according to results of the phase III SOLOIST-WHF* trial.

Participants in this multinational (32 countries) study were 1,222 patients aged 18–85 years (median age 70 years, 33.7 percent female, 93.2 percent White) with T2D who were treated with intravenous diuretics following a recent admission to hospital for worsening HF. They were randomized 1:1 to receive sotagliflozin (200 mg QD with potential increase to 400 mg) or placebo either before or within 3 days of hospital discharge.

Most patients (79.1 percent) had LVEF** <50 percent. Median eGFR**, HbA_1c, and NT-proBNP** levels were 49.7 mL/min/1.73 m², 7.1 percent, and 1799.7 pg/mL, respectively. About 85 percent were on glucose-lowering medications.

Patients were followed up for a median 9 months. About 49 percent of patients received their first dose of study drug before hospital discharge, while 51.2 percent received their first dose a median 2 days post-discharge.

CV-related deaths, hospitalizations, and urgent (first and subsequent) visits for HF occurred in fewer patients in the sotagliflozin than placebo group (51.0 vs 76.3 per 100 patient-years [PYs]; hazard ratio [HR], 0.67, 95 percent confidence interval [CI], 0.52–0.85; p<0.001). [AHA 2020, LBS 7; N Engl J Med 2021;384:117-128]

Subgroup analyses showed that the results were consistent regardless of age (< or ≥65 years), sex, renal function (eGFR < or ≥60 mL/min/1.73 m²), geographic enrolment region, LVEF (< or ≥50 percent), or timing of first dose of trial drug (pre- or post-discharge).

Secondary endpoint analysis showed a lower rate of hospitalizations and urgent visits for HF with sotagliflozin vs placebo (40.4 vs 63.9 per 100 PYs; HR, 0.64, 95 percent CI, 0.49–0.83; p<0.001). There were fewer CV-related deaths in sotagliflozin than placebo recipients (10.6 vs 12.5 per 100 PYs; HR, 0.84, 95 percent CI, 0.58–1.22; p=0.36), as well as deaths from any cause (13.5 vs 16.3 per 100 patient-years; HR, 0.82, 95 percent CI, 0.59–1.14).

Serious adverse events leading to discontinuation of trial drug occurred in a similar proportion of sotagliflozin and placebo recipients (3.0 percent vs 2.8 percent). Hypotension, urinary tract infection (UTI), and acute kidney injury (AKI) also occurred at comparable rates between sotagliflozin and placebo recipients (hypotension: 6.0 percent vs 4.6 percent; UTI: 4.8 percent vs 5.1 percent; AKI: 4.1 percent vs 4.4 percent). However, more sotagliflozin than placebo recipients experienced diarrhoea (6.1 percent vs 3.4 percent) and severe hypoglycaemia (1.5 percent vs 0.3 percent).

Another SGLT2i for HF?

“Accumulating evidence from randomized clinical trials supports the use of SGLT2*** inhibitors in patients who have stable HF (with or without diabetes) and a reduced ejection fraction. The current trial showed that initiation of SGLT2 inhibition before or shortly after discharge in patients who were hospitalized for worsening HF was also beneficial,” noted the authors.

Nonetheless, they cautioned that the early termination of the trial due to loss of funding may have led to certain limitations including the smaller than planned population and lack of statistical power to examine secondary endpoints.

“The results of the SOLOIST-WHF trial clearly support the rationale for the use of sotagliflozin – and perhaps other SGLT2 inhibitors – in patients who have just recovered from a bout of decompensated congestive HF,” commented Professors Frank Brosius and Per Vandvik from the University of Arizona, Tucson, Arizona, US, and Lovisenberg Diaconal Hospital, Oslo, Norway, respectively, in an editorial. [N Engl J Med 2021;384:179-181]

“Although this may not modify current practice to a great degree, it does address a pragmatic concern about when these agents can be safely used in patients with HF,” they added.