Reviwer: Dr. Muhammet Dural

Trial: Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction - PARAGON-HF

Published in Congress: ACC 2021

Full Text Link: https://www.nejm.org/doi/pdf/10.1056/NEJMoa1908655?articleTools=true, https://www.acc.org/sitecore/content/Sites/ACC/Home/Latest-in-Cardiology/Clinical-Trials/2019/08/30/21/24/PARAGON-HF,

Background: Heart failure with preserved ejection fraction (HFpEF) can lead to significant morbidity and mortality. Treatment options that can improve clinical outcomes in these patients are not as much as in low ejection fraction heart failure (HFrEF). Sacubitril–valsartan (S/V) has been shown to provide significant improvement in clinical outcomes in patients with HFrEF. The efficacy of S/V in patients with HFpEF was evaluated in PARAGON-HF study.

Objective : In PARAGON-HF study, it was aimed to evaluate the efficacy and safety of S/V in patients with HFpEF.

Method: Patients aged ≥50 years with NYHA class II-IV symptoms, ejection fraction ≥45%, elevated natriuretic peptide levels, and structural heart disease (left atrial enlargement or left ventricular hypertrophy) were enrolled to the study. Patients were randomized to either S/V (n = 2,419) versus valsartan (n = 2,403).

Results: The primary endpoint of the study, cardiovascular death or hospitalization rates for heart failure, was similar between the two groups. It was observed that the improvement in NYHA symptom classification, which is one of the secondary outcomes, was significantly higher in the S/V group (p < 0.05). Worsening renal function was observed in 1.4% in the S/V group and 2.7% in the valsartan group (p < 0.05). When evaluated in terms of gender differences, S/V was found to provide a significant reduction in primary outcomes in women [HR 0.73 (95% CI 0.59-0.90)]. However, this benefit could not be demonstrated in men [HR 1.03 (95% CI 0.84-1.25) (p for interaction = 0.017)].

Conclusion: S/V did not reduce cardiovascular death or hospitalization for heart failure when compared with valsartan in patients with HFpEF. Deterioration in renal function was less common in the S/V group. A reduction in primary outcomes was found in women with S/V, but not in men.

Interpretation: In this study, S/V was not found to be superior to valsartan in reducing cardiovascular death or hospitalizations for heart failure in patients with HFpEF. In terms of gender, it can be thought that it is more effective in women. In addition, it is clinically important that the deterioration in renal functions is less in the S/V group and that the improvement in NYHA symptom classification is more pronounced.