Benefits of sotagliflozin across the full range of baseline blood pressure in the SOLOIST-WHF Trial

Background Physicians remain hesitant to start SGLT inhibitors in patients with heart failure (HF) and “borderline” systolic blood pressure (SBP) due to concerns for precipitating hypotension and kidney injury. In SOLOIST-WHF, sotagliflozin initiated before or shortly after discharge was safe and effective. However, patients with the lowest baseline SBP have not been investigated. Purpose To evaluate the safety and efficacy of SGLT inhibition across the SBP spectrum among patients admitted with acute HF exacerbations. Methods The SOLOIST-WHF trial randomized 1222 patients with type 2 diabetes admitted for worsening HF to the dual SGLT 1 and 2 inhibitor, sotagliflozin or matching placebo. Patients were randomly assigned to treatment either in-hospital or ≤3 days post-discharge. Patients needed to demonstrate a baseline SBP ≥100 mmHg off inotropic therapy at screening, though the blood pressure in the present analysis was collected at the time of randomization and therefore patients with SBP<100 mmHg are included. The primary efficacy endpoint was total number of deaths from cardiovascular causes and hospitalizations or urgent visits for HF. Interaction testing was conducted between treatment effect and SBP, as well as in safety endpoints between those patients with higher SBP (≥ 110 mmHg) versus lower SBP (< 110 mmHg). Safety endpoints of interest include hypotension and acute kidney injury (AKI). Results Median blood pressure readings in the placebo and sotagliflozin arms were 122/72 and 122/73, respectively. Baseline heart rates in the placebo and sotagliflozin arms were 72 and 71, respectively. Based on cubic spline analysis, there was no difference in treatment risk ratio across the baseline SBP range from an SBP of ~90 to ~180 mmHg (p for interaction = 0.86; Figure). Of the patients with a baseline SBP <110 mmHg (n=201), those randomized to sotagliflozin had a significant reduction in total occurrences of cardiovascular deaths and HF-related events (HR 0.56 (95% CI 0.33-0.95), p=0.03). These data suggest efficacy of sotagliflozin in even the lowest SBP stratum (Table). There was no difference in the incidence of adverse events of hypotension (p=0.34) or AKI (p=0.69). Conclusion Treatment with sotagliflozin reduced the risk of CV death and HF-related events regardless of baseline SBP. Furthermore, initiation of sotagliflozin in patients with low SBP was not associated with an increased incidence of AKI and hypotension. These results support the initiation of SGLT inhibition during hospitalization even in heart failure patients with “borderline” SBP.