Efficacy of novel HF drug persists at lower doses

NATIONAL HARBOR, Md. — Patients with HF treated with lower doses of an angiotensin receptor-neprilysin inhibitor exhibited reductions in risk for CV-related death and HF hospitalization compared with patients treated with lower doses of enalapril, according to a new analysis of the PARADIGM-HF trial.

Researchers evaluated data collected from patients with HF and reduced ejection fraction enrolled in PARADIGM-HF. Patients were treated with the angiotensin receptor blocker valsartan bonded to the neprilysin inhibitor sacubitril (Entresto, Novartis; target dose, 200 mg twice daily) or the ACE inhibitor enalapril (target dose, 10 mg twice daily).

The trial was terminated early after valsartan/sacubitril was shown to significantly reduce the risk for the primary composite outcome of CV-related death or first incidence of HF-related hospitalization compared with enalapril.

The goal of the present analysis was to compare the effects ofvalsartan/sacubitril and enalapril when patients received doses lower than the study target as a result of dose reduction due to treatment intolerance.

According to results presented at the Heart Failure Society of America Annual Scientific Meeting, dose reduction occurred in 42% of the valsartan/sacubitril group and 43% of the enalapril group during the course of the study. Hypotension was the most cited reason for dose reduction in the valsartan/sacubitril group and cough in the enalapril group. Dose reduction was more common in patients who were older, sicker, had higher levels of serum creatinine and NT-proBNP at baseline, and had an implantable cardioverter defibrillator or cardiac resynchronization therapy device, according to Orly Vardeny, PharmD, MS, from the University of Wisconsin School of Pharmacy.

Patients who did not require dose reduction had significantly reduced risk for the primary outcome with valsartan/sacubitril compared with enalapril (HR = 0.79; 95% CI, 0.71-0.88; P < .001). However, patients treated with reduced-dose valsartan/sacubitril also had a significantly lower risk for events compared with patients treated with a similarly reduced dose of enalapril: valsartan/sacubitril dose of 100 mg to 200 mg vs. enalapril 5 mg to 10 mg (HR = 0.8; 95% CI, 0.67-0.94; P = .008); valsartan/sacubitril dose below 100 mg vs. enalapril less than 5 mg (HR = 0.76; 95% CI, 0.58-0.99; P = .043).

"Among those unable to remain on the target dose of either study drug, patients treated with [valsartan/sacubitril] still had a better outcome compared to those treated with enalapril," Vardeny said. "These data suggest that the efficacy of [valsartan/sacubitril] relative to enalapril was maintained even at lower than target doses."– by Adam Taliercio

Source: www.healio.com