Eplerenone Has Consistent Benefit for Different Durations of HF

Although eplerenone is consistently beneficial regardless of heart failure with reduced ejection fraction (HFrEF) duration, patients with longer-standing HFrEF have worse clinical status and more events, according to a study in the Journal of the American College of Cardiology.

The post hoc analysis of the EMPHASIS-HF (ClinicalTrials.gov Identifier: NCT00232180) trial assessed the efficacy and safety of eplerenone in patients based on HFrEF duration.

Participants were aged 55 years or older with New York Heart Association functional class II symptoms, left ventricular ejection fraction of 30% or less, and were being treated with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or both and a β-blocker (unless contraindicated) at the recommended dose or maximally tolerated dose.

Participants were randomly assigned to receive eplerenone (up to 50 mg daily) or placebo in addition to recommended therapy. HF duration was classified into 3 groups: less than 1 year, 1 to less than 5 years, and 5 years or longer. The primary outcome was the time to first occurrence of the composite of cardiovascular death or HF hospitalization.

The cohort included 2732 patients with HFrEF, mild symptoms, and data on HF duration. The median HF duration was 2.4 years (IQR, 0.4-7.0 years). The number of patients in each HF duration category was 975 (35.7%; mean age, 67.8±7.6 years) in the less than 1 year group, 769 (28.1%; mean age, 68.2±7.7 years) in the 1 to less than 5 years group, and 988 (36.2%; mean age, 69.8±7.5 years) in the 5 years or longer group. The median follow-up was 21 months. Patients who had a longer HF duration were more frequently men and older.

The incident rate per 100 patient-years of the composite of cardiovascular death or hospitalization for HF increased with greater HF duration. In the less than 1 year group it was 9.8 (95% CI, 8.4-11.4). In the 1 to less than 5 years group it was 13.5 (95% CI, 11.6-15.7). In the 5 years or longer group it was 17.6 (95% CI, 15.6- 19.8).

The benefit of eplerenone was consistent for all outcomes according to HF duration. The overall adjusted hazard ratio (HR) for eplerenone vs placebo for the primary outcome was 0.64 (95% CI, 0.54-0.76). For the less than 1 year group, the HR was 0.59 (95% CI, 0.42-0.82), for the 1 to less than 5 years group the HR was 0.72 (95% CI, 0.52-1.00), and in the 5 years or longer group, the HR was 0.59 (95% CI, 0.46-0.76; P_interaction =.54).

The number needed to treat (NNT) for the median trial duration regarding the primary outcome was 10 (95% CI, 8-14) for HF duration of 5 years or longer vs 14 (95% CI, 11-21) for HF duration of less than 1 year and 13 (95% CI, 10-19) for HF duration of 1 to less than 5 years. The NNT for all-cause mortality was 24 (95% CI, 15-95) for HF duration of 5 years or longer vs 34 (95% CI, 21-136) for HF duration of less than 1 year and 31 (95% CI, 19-125) for HF duration of 1 to less than 5 years.

The researchers noted that their study is not a prespecified analysis, and HF duration was obtained from questions on a case report form and was not independently verified. Also, the results may not be generalizable to all patients with HFrEF, and separate Cox regression analyses were conducted for each subpopulation based on HF duration, which may have affected the estimation of HRs.

“Eplerenone was efficacious and safe in patients with long-standing HFrEF, who obtained substantial reductions in mortality and morbidity with this treatment,” wrote the investigators. “MRA [mineralocorticoid receptor antagonist] treatment should be considered in all patients with HFrEF, regardless of the duration of HF.”

Disclosure: The EMPHASIS-HF trial was sponsored by Pfizer. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.