ACE inhibitor therapy significantly slowed myocardial fibrosis progression compared with no treatment in Duchenne or Becker muscular dystrophy patients (3.1% vs 10.0% increase in LV mass; P=.001).
RCT (n=76)
1:1
Yes
Does ACE inhibitor therapy reduce myocardial fibrosis progression in male patients with Duchenne or Becker muscular dystrophy with preserved LVEF and myocardial fibrosis?
In patients with Duchenne or Becker muscular dystrophy with preserved LVEF and myocardial fibrosis, early ACE inhibitor therapy significantly slows the progression of myocardial fibrosis.
Absolute Event Rate: 3.1% vs 10%
p-value: p=.001
Importance: In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival. Objective: To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR). Design, Setting, and Participants: A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non-intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016. Interventions: Randomization (1:1) to receive or not receive ACE inhibitor therapy. Main Outcomes and Measures: Primary outcome was MF progression from baseline to the 2-year CMR study. Results: Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient SE, -0.16 0.07; P = .03). Among patients with MF and preserved LVEF (42 55%), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean SD increase of 3.1% 7.4% vs 10.0% 6.2% as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient SE, -4.51 2.11; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 18.2% vs 0 of 21 0%; log-rank P = .04). Conclusions and Relevance: In this 2-year, follow-up, randomized clinical trial of patients with Duchenne or Becker muscular dystrophy whose LVEF was preserved and MF was present as determined on CMR, ACE inhibitor therapy was associated with significantly slower progression of MF. The presence of MF was associated with worse patient prognosis. Trial Registration: clinicaltrials.org Identifier: NCT02432885.
Silva et al. (Wed,) conducted a rct in Duchenne and Becker muscular dystrophy (n=76). ACE inhibitor therapy vs. no ACE inhibitor therapy was evaluated on Myocardial fibrosis progression from baseline to the 2-year CMR study (p=.001). ACE inhibitor therapy significantly slowed myocardial fibrosis progression compared with no treatment in Duchenne or Becker muscular dystrophy patients (3.1% vs 10.0% increase in LV mass; P=.001).