PARAGON-HF Misses Endpoint in Preserved Heart Failure, But Benefit Noted for Some Patients: Presented at ESC

By Walter Alexander

PARIS -- September 5, 2019 -- The benefit for sacubitril/valsartan compared with valsartan in reducing the risk of a first and/or recurrent heart failure hospitalisation and cardiovascular death narrowly missed statistical significance in the PARAGON-HF trial, researchers reported here at the 2019 European Society of Cardiology (ESC) Congress.

Benefits were more pronounced in patients with heart failure with preserved ejection fraction and in women, said Scott D. Solomon, MD, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts.

The PARAGON-HF study randomised 4,822 patients to receive sacubitril/valsartan or valsartan. Most patients in the study were already taking a renin-angiotensin system inhibitor. Patients were required to have signs and symptoms of heart failure, a left ventricular ejection fraction of ≥45 percent, evidence of natriuretic peptide elevation, and structural heart disease.

The primary endpoint was a composite of total (first and recurrent) heart failure hospitalisations and cardiovascular death.

The primary outcome occurred in 2,407 patients in the combination treatment group and in 2,389 patients in the valsartan monotherapy group (rate ratio, 0.87; 95% confidence interval, 0.753-1.005; P = .0585).

Stratified by gender, the rate ratios were 1.03 for males and 0.73 for females. Stratified by left ventricular ejection fraction, rate ratios were 0.78 at or below a median of 57% and 1.00 above a median of 57%.

Safety and tolerability were similar to that seen in the PARADIGM trial, but with more hypotension and less serum creatinine and potassium with sacubitril/valsartan compared with valsartan alone.

“These findings suggest that in this disease with no evidence-based therapy and huge unmet need, some patients with heart failure with preserved ejection fraction -- particularly those with ejection fractions below normal but not frankly reduced -- may benefit from sacubitril/valsartan.”

[Presentation title: Angiotensin Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: the PARAGON-HF Trial]

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