Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy—analysis of registry data

Abstract

Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Current Practices in Treating Cardiomyopathy and Heart Failure in Duchenne Muscular Dystrophy (DMD): Understanding Care Practices in Order to Optimize DMD Heart Failure Through ACTION

“…This approach is generally in keeping with what is outlined in the consensus guidelines [8,9]. Furthermore, the fact that the majority of providers (68%) are initiating prophylactic therapy with ACEi/ARB is notable given recent data demonstrating that prophylactic initiation is associated with higher survival and lower rates of heart failure hospitalization [6]. Initiation and use of aldosterone antagonists is more variable as just over half of providers routinely use this class of medication relatively early in the course of cardiomyopathy with the onset of LGE or systolic dysfunction.…”

“…These clinical gains have improved overall survival, but have "unmasked" the long term progression of cardiomyopathy to heart failure. Cardiac disease now accounts for ~ 30-50% of DMD-related mortality [5,6]. These mortality rates have led to sequential consensus guidelines discussing the evolving outcomes, diagnostic protocols, and approaches to medical therapy.…”

“…Despite these recommendations, and recent data suggesting cardiac disease progression may be modified through medical management, the indications for employing medical and advanced therapies remains heterogenous and generally insufficient [5,6,[10][11][12][13]. Only 43% of participants in the Cooperative International Neuromuscular Research Group (CINRG) with ventricular dysfunction were on any cardiac medications, and a recent multi-center study demonstrated only 57% of patients with severe dysfunction were on both an angiotensin-converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) and a beta-blocker [13,14].…”

Health Care Use of Cardiac Specialty Care in Children With Muscular Dystrophy in the United States

“…There is evidence to suggest that early implementation of ACEIs/ARBs and aldosterone antagonists may delay the decline of myocardial function, increase survival, and reduce heart failure hospitalization. 18 , 36 , 37 In a randomized, double‐blinded, placebo‐controlled study of patients with DMD, among patients with earlier use of ACEI, there were fewer cases of decreased ventricular function and reduced mortality. 18 , 38 In light of such findings, the 2018 DMD Care Considerations and American Heart Association guidelines suggest starting an ACEI or ARB around the age of 10 years for patients with DMD.…”

The year in cardiovascular medicine 2021: heart failure and cardiomyopathies

“…A large French registry showed that prophylactic treatment of patients without LV dysfunction with an ACE inhibitor was able to prevent the transition to HF and improve survival in Duchenne muscular dystrophy. 55 …”