Feasibility of Neurohumoral Blocker Withdrawal in Patients Optimally Responding to Cardiac Resynchronization Therapy: An Open-label, Double Randomized Controlled Pilot Trial

Abstract

Background It remains unclear if medical therapy remains necessary in HF patients with myocardial recovery after CRT in whom conduction delay is thought to be the main driver. Methods This was a prospective multicenter, open-label, double randomized pilot trial to investigate the safety of neurohumoral (NH) blocker withdrawal in HF patients with recovered ejection fraction (HFrecEF) after CRT. Subjects were randomized to systematic withdrawal of RAAS inhibitors and beta blockers (BB) versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling defined by an increase in left ventricular end systolic volume index (LVESVi) of more than 15% at 24 months. The secondary endpoint is a composite safety endpoint of all-cause mortality, HF related hospitalizations and incidence of sustained ventricular arrhythmias at 24 months. The primary analysis was by intention to treat. Results: Between September 24, 2014, and February 15, 2017, 80 subjects were consecutively enrolled and randomized between 4 groups (continuation of NH blocker therapy (n=20), withdrawal of RAAS inhibitors (n=20), withdrawal of BB (n=20) and withdrawal of RAAS inhibitors and BB (n=20)). Of the 80 subjects, 6 (7.5%) met the primary endpoint of recurrence of negative remodeling based on an increase of >15% in LVESVi. The secondary endpoint occurred in 4 subjects (5%) within 24 months. There was no difference between the 4 groups regarding the primary (log rank p=0.497) and secondary endpoint (log rank p=0.507) (Figure 1). There were no hospital admissions due to HF or cardiac deaths during this time period in any subject. However, re-initiation of therapy occurred in 16 (20%) subjects due to hypertension or supraventricular arrhythmias. Conclusion Compared to continuation, withdrawal of NH blockers in patients with myocardial recovery after CRT is not associated with a recurrence of LV dilatation or HF after 2 years. However, the feasibility of NH blocker withdrawal is hampered because of hypertension and supraventricular arrhythmias.