Hospitalization Risk and Beta-Blocker Therapy in HF with Preserved Ejection Fraction

Beta-blocker therapy in older outpatients with heart failure and preserved ejection fraction (HFpEF) is associated with higher risk for HF hospitalization as EF increases, according to study findings published in the Journal of the American College of Cardiology: Heart Failure.

Investigators aimed to explore the relationship between HF hospitalization and death in patients with HFmrEF or HFpEF receiving beta-blockers. They conducted a propensity score-adjusted real-world observational cohort study that included 435,897 older outpatients (≥65 years of age) in the United States (US) with HF and EF of 40% or greater. Data were deidentified and from the US PINNACLE Registry between 2013 and 2017. The investigators used multivariable Cox regression models to evaluate the associations between beta-blocker use and death, HF hospitalization, and the composite of death and HF hospitalization.

Among all included patients (HFpEF, 360,223; HFmrEF, 75,674) there were 289,377 patients (age, 76.2±7.8 years; 52.6% men; 71.9% White; 5.5% Black) using a beta-blocker at first encounter, although this was less common among patients with HFpEF vs HFmrEF (64.0% vs 77.7%; P <.001). There were 146,520 patients not using a beta-blocker at first encounter (age, 76.0±7.8 years; 50.5% men; 73.2% White; 5.1% Black). Of the patients receiving beta-blocker therapy, 70.8% had coronary artery disease, 86.2% had hypertension, 30.3% had diabetes mellitus, 45.6% had atrial fibrillation/flutter, 2.8±1.2 were receiving antihypertensive medications, and 72.7% were receiving a statin.

The investigators subsequently excluded 29,894 patients with nonoverlapping propensity scores. Except for sex, prior coronary artery bypass surgery, number of antihypertensive medications, use of statin, systolic blood pressure, prior percutaneous coronary intervention, and coronary artery disease, all other standardized differences were less than 10%.

In adjusted models, there were significant interactions between beta-blocker therapy and left ventricular ejection fraction (LVEF) for death, HF hospitalization, and the composite of death/HF hospitalization (all P <.001). As EF increased, the risk related to beta-blocker use increased, although in patients with HFmrEF, beta-blockers were associated with decreased risk of death and HF hospitalization.

There was a higher risk of HF hospitalization and lack of survival benefit in patients with HFpEF (≥40%), noticeably in patients with EF of greater than 60%. They found no significant 3-way interactions between beta-blocker use, LVEF, and hypertension (P_interaction =.97; P =.51), atrial fibrillation (P_interaction =.17; P =.60), or myocardial infarction (P_interaction =.18; P =.18).

Study limitations include a lack of confirmatory randomized data, as well as inclusion of only patients that were aged at least 65 years. Additionally, cause of death was not discernable by investigators.

“In a large, real-world, propensity score-adjusted cohort of older patients with HF and LVEF 40% or greater, beta-blockers were associated with a higher risk of HF hospitalization as LVEF increased,” the investigators concluded. “There was evidence of potential benefit for HF hospitalization and death in patients with HFmrEF, but in patients with higher LVEF (particularly >60%), there was a lack of survival benefit and a higher risk of HF hospitalization associated with the use of beta-blockers.” Due to the potentially higher risk of adverse outcomes in patients with HFpEF, the investigators urge careful consideration in the use of beta-blockers in this patient population.