Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study)

Abstract

Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).

Trial registration: ClinicalTrials.gov NCT02045043.

Figure 1

Freedom from appropriate ICD shock in ACEi/ARB versus No-ACEi/ARB patient subcohorts: All patients (left) and propensity matched sub-cohorts (right). Numbers in brackets represent the number of patients in each group. p-value represents log rank significance level ACEi (angiotensin converting enzyme inhibitor); ARB (angiotensin receptor blocker); ICD (implantable cardiac defibrillator)

Figure 2

Freedom from appropriate ICD shock in ACEi/ARB versus No-ACEi/ARB in matched patient subcohorts stratified by glomerular filtration rate. ACEi (angiotensin converting enzyme inhibitor); ARB (angiotensin receptor blocker); GFR (glomerular filtration rate); ICD (implantable cardiac defibrillator).

Figure 3

Freedom from appropriate ICD shock in ACEi/ARB versus No-ACEi/ARB in matched patient subcohorts stratified to Ischemic versus Non ischemic cardiomyopathy. Numbers in brackets represent the number of patients in each group. p-value represents log rank significance level ACEi (angiotensin converting enzyme inhibitor); ARB (angiotensin receptor blocker); ICD (implantable cardiac defibrillator) GFR (glomerular filtration rate).

Figure 4

Freedom from appropriate ICD shock in ACEi/ARB versus No-ACEi/ARB in matched patient subcohorts stratified by indication for device implantation. ACEi (angiotensin converting enzyme inhibitor); ARB (angiotensin receptor blocker); ICD (implantable cardiac defibrillator).