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Original Investigation
November 19, 2014

Association Between Use of β-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

Author Affiliations
  • 1Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
  • 3Department of Clinical Science and Education, Karolinska Institutet, South Hospital, Stockholm, Sweden
  • 4Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
  • 5Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
  • 6Department of Cardiology, Danderyd Hospital, Stockholm, Sweden
JAMA. 2014;312(19):2008-2018. doi:10.1001/jama.2014.15241

Importance  Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). β-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF.

Objective  To test the hypothesis that β-blockers are associated with reduced all-cause mortality in HFPEF.

Design  Propensity score–matched cohort study using the Swedish Heart Failure Registry. Propensity scores for β-blocker use were derived from 52 baseline clinical and socioeconomic variables.

Setting  Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012.

Participants  From a consecutive sample of 41 976 patients, 19 083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for β-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22 893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients.

Exposures  β-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable.

Main Outcomes and Measures  The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization.

Results  Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). β-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P = .46). In the matched HFREF cohort, β-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P = .001).

Conclusions and Relevance  In patients with HFPEF, use of β-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. β-Blockers in HFPEF should be examined in a large randomized clinical trial.