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Association Between Use of β-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Study Questions:
What is the impact of beta-blockers on mortality in patients with diastolic heart failure?
Methods:
The study cohort was comprised of 19,083 heart failure patients with preserved ejection fractions from a total sample of 41,976 patients participating in the Swedish Heart Failure Registry. The mean age was 76 ± 12 years and 46% were women. Fifty-two baseline clinical and socioeconomic variables were used to derive propensity scores for beta-blocker utilization. A total of 8,244 diastolic heart failure patients were matched 2:1 based on age and propensity score to yield 5,496 treated and 2,748 untreated patients. The study investigators conducted a positive-control consistency analysis involving 22,893 patients with systolic heart failure, of whom 6,081 were matched yielding 4,054 treated and 2,027 untreated patients. The study investigators used two methods to analyze beta-blockers prescribed at discharge from the hospital or during an outpatient visit: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. All-cause mortality was the prespecified primary outcome, and combined all-cause mortality or heart failure hospitalization was the secondary outcome.
Results:
The median follow-up period was 755 days in patients with diastolic heart failure, and 709 days in the matched cohort. No patients were lost to follow-up. The investigators found that the 1-year survival in the matched diastolic heart failure cohort was 80% versus 795 in the untreated patients, and 5-year survival was 45% versus 42%, with 41% (n = 2,279) versus 45% (n = 1,244) and 177 versus 191 deaths per 1,000 patient- years (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86-0.996; p = 0.04). They found that beta-blockers were not associated with reduced combined mortality or heart failure hospitalizations: 61% (n = 3,368) versus 64% (n = 1,753) total for first events, with 371 versus 378 first events per 1,000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; p = 0.46). However, in the matched systolic heart failure cohort, the investigators found that beta-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97; p = 0.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; p = 0.001).
Conclusions:
The authors concluded that in patients with diastolic heart failure, beta-blockers were associated with lower all-cause mortality, but not with combined all-cause mortality or heart failure.
Perspective:
Although this was an observational study, the finding that beta-blockers are associated with lower all-cause mortality in diastolic heart failure is important. The MERIT-HF (Lancet 1999;353:2001-7) study reported that sudden death is more common in NYHA class I and II systolic heart failure patients, suggesting that beta-blockers may benefit in these patients as a result of their anti-arrhythmic properties in addition to the benefits of reverse-remodeling. Similar mechanisms may be true for diastolic heart failure patients. The benefit of beta-blockers in diastolic heart failure suggested by the findings of this study, as the authors point out, must now be evaluated in a double-blind randomized clinical trial. Also, data are needed to determine whether the benefit of beta-blockade in diastolic heart failure is good for both ischemic and nonischemic etiologies.
Keywords: Follow-Up Studies, Heart Failure, Diastolic, Adrenergic beta-Antagonists, Confidence Intervals, Heart Failure, Systolic, Hospitalization, Death, Sudden, Cardiac, AHA Annual Scientific Sessions
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