Most Clinically Stable Heart Failure Patients Benefit From Sacubitril/Valsartan

Patients who are clinically stable benefited as much from sacubitril/valsartan as patients who were more recently hospitalized.

Clinically stable patients without prior heart failure hospitalization were likely to benefit from sacubitril/valsartan as much as more recently hospitalized patients, according to recent data published in JACC: Heart Failure.

In addition, patients with  recent heart failure who required hospitalization were more likely to experience a cardiovascular death or HF hospitalization than those who had never been hospitalized.

Sacubitril/valsartan reduced death and heart failure hospitalization in patients with class II-IV HF with reduced ejection fraction in the PARADIGM-HF trial, although recent data have suggested that switching from an angiotensin-converting enzyme (ACE) inhibitor should be delayed until clinical decompensation.

Scott D. Solomon, MD, from the Cardiovascular Division at Brigham and Women’s Hospital in Boston, and colleagues sought to assess whether the benefit of sacubitril/valsartan varied with clinical stability.

“We find that while the more remote a heart failure hospitalization, the lower the overall risk, there was no evidence that these most stable patients benefit less than the least stable patients,” the researchers wrote. “These results should help inform clinicians who might consider switching patients with heart failure from standard RAS [renin angiotensin system] inhibitors to sacubitril/valsartan.”

In the PARADIGM-HF study, patients received enalapril at a dose of 10 mg twice daily for 2 weeks, followed by sacubitril/valsartan, first dosed at 100 mg twice daily, then 200 mg twice daily for 4 to 6 weeks. They were followed for a median of 27 months.

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Therefore, Dr Solomon and colleagues compared outcomes among 1611 patients with prior hospitalization within 3 months of screening, 1009 patients between 3 and 6 months of screening, 886 patients between 6 and 12 months of screening, 1746 patients after more than 12 months of screening, and 3125 patients who had never been screened.

They found that 20% of patients without prior heart failure hospitalization experienced cardiovascular death or heart failure hospitalization during the course of the trial. The risk of cardiovascular death or heart failure hospitalization was higher in patients with more recent hospitalizations compared with those without prior hospitalizations (<3 month hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.29-1.66; 3-6 month HR: 1.46; 95% CI: 1.26-1.69; 6-12 month HR: 1.29; 95% CI: 1.10-1.51; >12 month HR: 1.26; 95% CI: 1.12-1.43; P for trend <.001).

Compared with enalapril, the efficacy of sacubitril/valsartan was not significantly different, based on the presence or timing of prior hospitalization for heart failure (P=.16 for heart failure hospitalization, P=.66 for cardiovascular death, and P=.89 for all-cause death).

“While large heart failure trials are often designed to assess the effectiveness and safety of therapies in a broad group of patients, the spectrum of patients in clinical practice can be broader still,” Dr Solomon and colleagues noted.

“Further research on broader populations incorporating patients who may not have been eligible for PARADIGM-HF is necessary to fully appreciate the safety and efficacy of sacubitril/valsartan in the full spectrum of heart failure patients.”


Solomon SD, Claggett B, Packer M, et al. Efficacy of sacubitril/valsartan relative to a prior decompensation: the PARADIGM-HF trial. JACC Heart Fail. 2016. doi:10.1016/j.jchf.2016.05.002.