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

Heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, particularly with the aging of the population. HFpEF is associated with high morbidity and mortality, with poor quality of life and high rate of heart failure rehospitalization. In HFpEF previous studies failed to reach a positive outcome. There is currently no approved treatment for HFpEF. The overall the PARAGON-HF trial population showed a 13% reduction in the primary endpoint (cardiovascular death and total heart failure hospitalizations) with sacubitril/valsartan treatment vs 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 brings benefits compared with valsartan alone. Results of the PARAGON-HF revealed that HFpEF patients with certain clinical profiles (lower strata of EF below 57% and women), for whom no evidence-based therapy is available, may benefit from treatment with sacubitril/valsartan. In the paper the comments to the PARAGON-HF results are presented and a mechanistic discussion is also provided.