A Randomised, Placebo-controlled Trial of Carvedilol in Early Familial Dilated Cardiomyopathy

• Published in: Heart, lung & circulation lung & circulation, 2011-09, Vol.20 (9), p.566-573
• Main Authors: Yeoh, Thomas, MBBS, PhD, Hayward, Christopher, MD, Benson, Victoria, MSc, Sheu, Angela, Richmond, Zara, BSc, Feneley, Michael P., MD, Keogh, Anne M., MD, Macdonald, Peter, MD, PhD, Fatkin, Diane, MD
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - adverse effects; Adult; Beta blocker; Carbazoles - administration & dosage; Carbazoles - adverse effects; Cardiomyopathy, Dilated - diagnostic imaging; Cardiomyopathy, Dilated - drug therapy; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - physiopathology; Cardiovascular; Early disease; Echocardiography; Familial dilated cardiomyopathy; Female; Heart Ventricles - diagnostic imaging; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Humans; Male; Middle Aged; Organ Size; Propanolamines - administration & dosage; Propanolamines - adverse effects; Time Factors
• ISSN: 1443-9506; 1444-2892
• DOI: 10.1016/j.hlc.2011.06.004

Background Screening of asymptomatic relatives of patients with dilated cardiomyopathy (DCM) has identified a population of individuals with left ventricular dilatation and/or minimally impaired contraction who are believed to have early disease. A proportion of these individuals with early disease progress to overt cardiomyopathy, however to our knowledge there have been no studies that have examined the impact of early intervention on disease progression. Methods We evaluated 424 asymptomatic relatives in 110 families of probands with DCM and identified 102 individuals (24%) with suspected “early disease” (EDCM). Thirty-two EDCM subjects were randomised into a six-month placebo-controlled trial of the β-blocker, carvedilol. Transthoracic echocardiography and plasma nt-proBNP levels were measured at baseline and repeated at six months. The primary trial endpoint was change in left ventricular end-systolic diameter after six months. Subjects completing six months of blinded trial therapy were offered open-label carvedilol and then observed over an extended period with repeated clinical evaluation and echocardiography. Results At baseline, left ventricular dimensions, systolic function and plasma nt-proBNP levels were similar in carvedilol and placebo groups. There were no significant changes observed in these parameters in either treatment group after six months, however reductions in end-diastolic diameter (% predicted) were observed in carvedilol-treated subjects ( P = 0.002) during an open-label median follow-up of 32 months (range: 13–56 months). Conclusions In an asymptomatic population of individuals with EDCM, treatment with carvedilol for six months had no effect on echocardiographic left ventricular dimensions or systolic function, however longer-term treatment may reverse left ventricular remodelling (Australian Clinical Trials Registry N012605000204640).