Beta-blocker withdrawal to enhance exercise capacity in heart failure?

Spanish researchers assessed the effect of β-blocker discontinuation in patients with heart failure with preserved ejection fraction (HFpEF) on functional capacity in the phase 4 PRESERVE-HR study. They found a significant short-term amelioration of peak oxygen consumption (peak VO₂).

Prof. Julio Nuñez Villota (University Clinical Hospital of Valencia, Spain) explained that within the multiple pathophysiological mechanisms that are implicated in the heterogeneous syndrome of HFpEF, chronotropic incompetence plays a crucial role in some patients [1]. “Despite the lack of robust evidence, most HFpEF patients are currently treated with renin-angiotensin-aldosterone system (RAAS) inhibitors or β-blockers,” he stated. In recent large HFpEF trials, 70–80% of patients received β-blocker medication [2]. With this in mind, the aim of the PRESERVE-HR trial (NCT03871803) was to assess whether β-blocker withdrawal would lead to a short-term improvement in functional capacity in patients with HFpEF [1].

The crossover, investigator-blinded, randomised PRESERVE-HR trial included 52 patients with a left ventricular ejection fraction (LVEF) ≥50% and an N-terminal pro B-type natriuretic peptide (NT-proBNP) of >125 pg/mL. Furthermore, all subjects had had a previous hospital admission for acute heart failure, were stable on β-blockers for ≥3 months, and had established chronotropic incompetence with an index of <0.62. Exclusion criteria included a resting heart rate of over 75 at screening. Baseline characteristics showed a mean age of 74.5 years, 59.6% women, 88.5% patients with hypertension, 34.6% in NYHA class III or IV, mean LVEF was 64.7%, and median NT-proBNP 400 pg/mL [1]. “Regarding the exercise test parameters, the mean peak VO₂ was 12.5 mL/kg/min, percentage of predicted peak VO₂ was approximately 72%, and the chronotropic index was 0.41, reflecting chronotropic incompetence. Importantly, there were no significant differences between both treatment arms,” commented Prof. Nuñez.

All participants underwent cardiopulmonary exercise testing (CPET) with cycle-ergometry at days 0, 15, and 30 of the trial. Study arm A started with β-blocker withdrawal and crossed over to a re-introduction of β-blocker therapy after 15 days, while arm B stayed on β-blockers for the first part of the study and withdrew β-blockers in the second part. The primary endpoint was defined as change from baseline peak VO₂ and percentage of predicted peak VO₂. Among the secondary endpoints were differences in biomarkers, health status assessment, cognitive function, and specific echocardiographic measures [1,3].

1. 
   
   1. Nuñez Villota J. Effect on Maximal Functional Capacity of Betablockers Withdrawal in Heart Failure with Preserved Ejection Fraction and Chronotropic Incompetence: PRESERVE-HR trial. LBT 3, Heart Failure and World Congress on Acute Heart Failure 2021, 29 June–1 July.
   2. Meyer M, et al. Circ Heart Fail. 2019;12(8):e006213.
   3. Palau P, et al. Clin Cardiol. 2020;43(5):423-429.

 

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Posted on 19 August, 202120 August, 2021