PO-628-03 ASSOCIATION OF MINERALOCORTICOID RECEPTOR ANTAGONIST USE WITH MORTALITY AND VENTRICULAR ARRHYTHMIA RISK IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Abstract

Heart failure (HF) patients with implantable devices have improved outcomes on optimal Guideline-Directed Medical Therapy (GDMT), yet few studies have evaluated the impact of mineralocorticoid receptor antagonists (MRA) on mortality and arrythmia risk in patients who may be unable to tolerate optimal GDMT. To assess the impact of MRA use on the risk of all-cause mortality and ventricular tachyarrhythmia (VTA) in HF patients with an ICD or CRT-D who were not concomitantly treated with both beta blockers (BB) and ACE-inhibitors/angiotensin receptor blockers (ACE/ARB) in 4 MADIT (Multicenter Automatic Defibrillator Implantation Trial; MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK) and Ranolazine in High-Risk Patients with ICD (RAID) clinical trials. We included 5504 patients enrolled in 5 landmark ICD clinical trials. Patients were categorized by MRA use in addition to baseline BB and/or ACE/ARB use into subgroups of those who were prescribed both BB and ACE/ARB (2-drug GDMT) and those who were prescribed only one of the two drugs (1-drug GDMT) at enrollment. Cox proportional hazards regression models and Fine and Gray regression models, stratified by studies, were performed to assess the association between time-dependent MRA use and risks of all-cause mortality and VTA. VTA was defined as any treated or monitored sustained ventricular tachycardia (≥170 bpm) or ventricular fibrillation. Among 5504 study patients, 4392 (80%) were prescribed 2-drug GDMT and 1016 (18%) were prescribed 1-drug GDMT. MRA was prescribed to 1656 (30%) patients. Multivariate analysis demonstrated that MRA use was associated with a 52% reduction in mortality risk when prescribed in patients on 1-drug GDMT (HR=0.48 [95% CI: 0.27-0.86], p=0.014). The mortality benefit of MRA therapy was attenuated among patients on 2-drug GDMT (HR=1.05 [95% CI: 0.82-1.34], p=0.7) (Figure 1). Further, MRA use was associated with a 36% reduction in VTA risk in patients on 1-drug GDMT (HR=0.64 [95% CI: 0.40-1.01], p = 0.05), while among patients on 2-drug GDMT the association of MRA use with VTA risk was also attenuated (HR=1.09 [95% CI: 0.93-1.29], p=0.28) (Figure 2). In HF patients with an ICD or CRT-D who are unable to tolerate 2-drug GDMT, MRA use is associated with a reduction in the risk of mortality and VTA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)