Heart failure with preserved ejection fraction after the PARAGON-HF trial results: current knowledge and future directions

Heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, particularly in the context of the aging of the population. HFpEF is associated with high morbidity, mortality, and rate of heart failure rehospitalization as well as poor quality of life. Previous studies on HFpEF failed to reach a positive outcome. There is currently no approved treatment for HFpEF. The overall PARAGON‑HF trial population showed a 13% reduction in the primary endpoint (cardiovascular death and total heart failure hospitalizations) with sacubitril / valsartan treatment as compared with valsartan, which was of borderline statistical significance. Analyses of the secondary endpoints, including the clinical status, quality of life, and kidney function, imply that sacubitril / valsartan offers benefits compared with valsartan alone. The results of the PARAGON‑HF trial revealed that patients with HFpEF and particular clinical profiles (lower strata of ejection fraction below 57% and female sex), for whom no evidence‑based therapy is available, may benefit from treatment with sacubitril / valsartan. This review article summarizes opinions on the PARAGON‑HF results as well as a mechanistic discussion.