Key result
Withdrawing neurohumoral blockers post-CRT yields a low ~8% negative remodeling rate despite frequent comorbidity-driven re-initiation.
Why the study?
The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear.
Does withdrawal of neurohumoral blockers increase recurrence of negative remodeling in patients with normalized ejection fractions after cardiac resynchronization therapy?
RCT (n=80)
Open-label
2 × 2 factorial
Does withdrawal of neurohumoral blockers increase recurrence of negative remodeling in patients with normalized ejection fractions after cardiac resynchronization therapy?
Withdrawal of neurohumoral blockers in patients with normalized EF after CRT had low rates of negative remodeling recurrence, but was frequently hampered by the need to treat hypertension or supraventricular arrhythmias.
Answers are grounded in this paper and cite their sources.
May support selective withdrawal in post-CRT recovered EF; pilot RCT leaves open routine deprescribing pending larger trials given frequent re-initiation for comorbidities.[[1]](https://www.jacc.org/doi/10.1016/j.jacc.2020.01.040)[[2]](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.
BACKGROUND The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear. OBJECTIVES The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy. METHODS In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months. RESULTS Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias. CONCLUSIONS The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822).
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Nijst et al. (2020) conducted an RCT in Heart failure with normalized ejection fraction after cardiac resynchronization therapy (n=80). Withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers vs. Continuation of neurohumoral blocker therapy was evaluated on Recurrence of negative remodeling (increase in left ventricular end-systolic volume index of >15% at 24 months). Withdrawal of neurohumoral blockers after CRT resulted in a low 7.5% overall incidence of negative remodeling at 24 months, though 17 of 80 patients required re-initiation due to comorbidities.
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