title: Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy.
abstract: OBJECTIVE
  Duchenne and Becker muscular dystrophies (DBMD) are allelic disorders caused by mutations in dystrophin. Adults with DBMD develop life-threatening cardiomyopathy. Inhibition of phosphodiesterase 5 (PDE5) improves cardiac function in mouse models of DBMD. To determine whether the PDE5-inhibitor sildenafil benefits human dystrophinopathy, we conducted a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, number NCT01168908).
  
  
  METHODS
  Adults with DBMD and cardiomyopathy (ejection fraction ≤ 50%) were randomized to receive sildenafil (20mg 3× daily) or placebo for 6 months. All subjects received an additional 6 months of open-label sildenafil. The primary endpoint was change in left ventricular end-systolic volume (LVESV) on cardiac magnetic resonance imaging. Secondary cardiac endpoints, skeletal muscle function, and quality of life were also assessed.
  
  
  RESULTS
  An interim analysis (performed after 15 subjects completed the blinded phase) revealed that 29% (4 of 14) of subjects had a ≥10% increase in LVESV after 6 months of sildenafil compared to 13% (1 of 8) of subjects receiving placebo. Subjects with LVESV > 120ml at baseline were more likely to worsen at 12 months regardless of treatment assignment (p = 0.035). Due to the higher number of subjects worsening on sildenafil, the data and safety monitoring board recommended early termination of the study. There were no statistically significant differences in outcome measures between treatment arms.
  
  
  CONCLUSIONS
  Due to the small sample size, comparisons between groups must be interpreted with caution. However, this trial suggests that sildenafil is unlikely to improve cardiac function in adults with DBMD.
authors.affiliation: Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Doris G
authors.initials: DG
authors.lastname: Leung
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Herzka
authors.forename: W Reid
authors.initials: WR
authors.lastname: Thompson
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Genila
authors.initials: G
authors.lastname: Bibat
authors.forename: Gihan
authors.initials: G
authors.lastname: Tennekoon
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.forename: Karl H
authors.initials: KH
authors.lastname: Schuleri
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lardo
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: Richard E
authors.initials: RE
authors.lastname: Thompson
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D002302:Cardiac Output / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D004311:Double-Blind Method; D016189:Dystrophin / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D016037:Single-Blind Method; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D016189:Dystrophin; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate