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The 5-year estimated number needed to treat (NNT) for sacubitril/valsartan (Entresto) in the PARADIGM-HF trial was on par with that from other pivotal trials in heart failure with reduced ejection fraction (HFrEF), researchers found.

The angiotensin receptor-neprilysin inhibitor (ARNI) had a 5-year estimated NNT of 14 for the primary outcome of cardiovascular death or heart failure hospitalization vs an ACE inhibitor alone, with a range from 12 to 19 among subgroups.

For all-cause mortality, the estimated NNT was 21 to save one life over 5 years compared with enalapril. It was 11 compared with an imputed placebo, reported Gregg Fonarow, MD, of the University of California Los Angeles, and colleagues in .

For comparison, the NNT for 5-year all-cause mortality with other well-established HFrEF treatments in their landmark trials vs controls were as follows:

• 18 for ACE inhibitors
• 24 for angiotensin receptor blockers
• 8 for beta-blockers
• 15 for mineralocorticoid antagonists
• 14 for implantable cardioverter defibrillator
• 14 for cardiac resynchronization therapy

These findings "overall and for clinically relevant subpopulations are comparable with those of other well-established HF interventions and are better than those of commonly prescribed drugs for primary prevention," the researchers wrote. "These data support the current guideline recommendations for ARNI therapy for eligible patients with HFrEF."

Previous reports have highlighted the short-term risk declines for the PARADIGM-HF study group, yet the long-term, 5-year follow up of the absolute risk reduction and NNT findings have not been published, Fonarow and colleagues highlighted.

This paper should make clinicians more comfortable widening the target population, commented Paul Mather, MD, of University of Pennsylvania Perelman School of Medicine in Philadelphia.

"We know it's improved mortality in the PARADIGM-HF trial, and we also know that... its efficaciousness in the target heart failure with reduced ejection fraction population is similar to other standard proven therapies," Mather said to 番茄社区.

The researchers evaluated 8,399 HFrEF patients (mean age 63.8 and ejection fraction ≤ 40%), of whom 21.8% were women and 66.0% were white. Patients were randomized to sacubitril-valsartan or enalapril.

The investigators used data from the PARADIGM-HF trial cohort to calculate approximated overall and subpopulation 5-year NNT values.

The limitation is the natural methodology used to calculate NNT and the projected risk over 1 to 5 years, but this is a speed bump not a hurdle, according to Mather.

Looking ahead, Mather suggested following up longer to see if the implications carry out in about 10 years.