The rate ratio for the primary endpoint was 0.87 (95% confidence interval 0.75–1.01 p = 0.059).
The primary endpoint was a composite of total (first and recurrent) heart failure hospitalisations and cardiovascular death. Patients were required to have signs and symptoms of heart failure, a left ventricular ejection fraction of 45% or greater, evidence of natriuretic peptide elevation, and structural heart disease. The comparator was valsartan because most HFpEF patients already take a renin-angiotensin system inhibitor. A total of 4,822 patients were randomly assigned to sacubitril/valsartan or valsartan. PARAGON-HF was designed to test the hypothesis that sacubitril/valsartan would improve outcomes in HFpEF. The drug reduced morbidity and mortality in patients with HFrEF in the PARADIGM-HF trial.(3) It has a class I guideline recommendation for the treatment of HFrEF.(4) Sacubitril/valsartan, which combines the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, simultaneously inhibits the renin-angiotensin system and augments endogenous vasoactive peptide systems. Evidence-based therapies exist only for heart failure with reduced ejection fraction (HFrEF ejection fraction 40% or less). This encompasses heart failure with mid-range ejection fraction (HFmrEF ejection fraction 40–49%), and HFpEF (ejection fraction 50% or greater). Up to 15 million people in Europe and 64 million worldwide have heart failure – of these approximately half have left ventricular ejection fraction of 40% or greater. The PARAGON-HF results suggest that the impact of treatment may also vary.” “We’ve known for some time that patients with this disorder have different characteristics and aetiologies. Solomon of Brigham and Women’s Hospital, Harvard Medical School, Boston, US. “Our data strongly imply that one size might not fit all in HFpEF,” said co-principal investigator Professor Scott D. The PARAGON-HF trial showed evidence of a heterogeneous response to treatment, with potential benefit in certain subgroups, such as women and patients with an ejection fraction below the median. The late breaking results of the PARAGON-HF trial are presented in a Hot Line Session today at ESC Congress 2019 together with the World Congress of Cardiology (1) and published in the New England Journal of Medicine.(2) Paris, France – 1 Sept 2019: The angiotensin neprilysin inhibitor sacubitril/valsartan missed its primary endpoint of reducing total hospitalisation and cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF), but the data suggest there may be benefit in some patient groups.