Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction

J Am Coll Cardiol. 2021 Nov 23;78(21):2042-2056. doi: 10.1016/j.jacc.2021.08.073.

Abstract

Background: Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence.

Objectives: This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence.

Methods: This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used.

Results: The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively).

Conclusions: β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39).

Keywords: HFpEF; chronotropic incompetence; crossover trial; heart rate; peak Vo(2); percentage of predicted peakVo(2); β-blockers.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Aged
  • Aged, 80 and over
  • Cross-Over Studies
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Male
  • Single-Blind Method
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology*
  • Withholding Treatment* / trends

Substances

  • Adrenergic beta-Antagonists

Associated data

  • ClinicalTrials.gov/NCT03871803