Structural abnormalities and effects of sacubitril/valsartan in patients with mildly reduced or preserved ejection fraction and worsening heart failure: The PARAGLIDE-HF trial

Background: PARAGLIDE-HF showed significantly greater reduction in NT-proBNP in patients with LVEF>40% and worsening HF with sacubitril/valsartan (sac/val) vs valsartan (val). The impact of structural abnormalities on the effects of sac/val in this context is unknown. This study aimed to evaluate the impact of left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) on sac/val in patients with LVEF>40% and worsening HF. Methods: PARAGLIDE-HF patients were classified into 3 groups according the degree of structural abnormalities using LVH and LAE. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8. Secondary endpoints were recurrent cardiovascular composite events (HF hospitalizations, urgent HF visits, cardiovascular death) and adverse events (symptomatic hypotension, hyperkalemia, worsening renal function). Results: Of 454 (97.4%) patients with LVH and LAE data, 157 (34.5%) had both LVH and LAE, 178 (39.2%) had either LVH or LAE, and 119 (26.2%) had neither LVH nor LAE. Greater reduction in NT-proBNP with sac/val vs val was consistent across groups (P interaction = 0.705). There was no significant interaction between treatment and degree of structural abnormalities for other efficacy endpoints. Patients with both LVH and LAE had significantly higher odds of hyperkalemia with sac/val (OR 2.41, P interaction = 0.024). Conclusion: Patients with LVEF>40% and recent WHF had greater reduction in NT-proBNP with sac/val vs val, regardless of the degree of structural abnormalities. There was no difference in the effects of sac/val on efficacy endpoints across structural abnormality group. Patients with both LVH and LAE had higher odds for hyperkalemia with sac/val.