Beta-blockers in heart failure patients with preserved ejection fraction may lower all-cause mortality

Use of beta-blockers in patients with heart failure with preserved ejection fraction (HFPEF) was associated with lower all-cause mortality but not with consistent reductions in the combined outcome of mortality and heart failure hospitalization, an observational cohort study found.

Researchers conducted a propensity score-matched cohort study using a consecutive sample of 41,976 patients registered in the Swedish Heart Failure Registry to assess 52 clinical and socioeconomic variables. The registry tracked patients from 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden from July 2005 to December 2012. There were 19,083 patients with HFPEF (heart failure and an ejection fraction of at least 40%). Of these, 8,244 were matched 2:1 based on age and propensity score for beta-blocker use (5,496 treated and 2,748 untreated patients with HFPEF). A positive-control consistency analysis was also performed involving 22,893 patients with heart failure with reduced ejection fraction (HFREF); of these, 6,081 were matched (4,054 treated and 2,027 untreated patients).

Study results were published online Nov. 16 by the Journal of the American Medical Association.

Survival at 1 year among those who took beta-blockers was 84% (95% CI, 83% to 85%) compared to 78% (95% CI, 76% to 79%) among those who did not. At 5 years, survival among those on beta-blockers was 51% (95% CI, 50% to 52%) compared to 41% (95% CI, 39% to 44%) in non-users. The unadjusted hazard ratio (HR) for mortality throughout follow-up was 0.73 (95% CI, 0.69 to 0.77; P<0.001).

In the matched HFPEF cohort, 1-year survival was 80% in treated patients versus 79% for untreated patients, and 5-year survival was 45% and 42%, respectively, with 177 deaths per 1,000 patient-years in the treated group compared to 191 deaths per 1,000 patient-years in the untreated group (HR, 0.93; 95% CI, 0.86 to 0.996; P=0.04). Beta-blockers were not associated with a reduction in the combined outcome of mortality and heart failure hospitalizations: 371 vs. 378 first events per 1,000 patient-years (HR, 0.98; 95% CI, 0.92 to 1.04; P=0.46). In the matched HFREF cohort, beta-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82 to 0.97, P=0.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84 to 0.95; P=0.001).

The use of beta-blockers in HFPEF should be examined in a large randomized clinical trial, the authors noted, an observation mirrored by an accompanying editorial, which described using an administrative database to probe the potential efficacy of a therapy as “a mismatch of the data to the question.”

The editorialists noted that while the national registry could capture information across a large population, more than half the patients in this case were excluded from the primary analysis. “That a large number of individuals treated with [beta]-blockers could not be matched to patients not treated with [beta]-blockers on propensity score indicates the presence of a strong selection bias in [beta]-blocker prescribing patterns,” the editorialists wrote.