Effects of atenolol, perindopril and verapamil on haemodynamic and vascular function in Marfan syndrome - a randomised, double-blind, crossover trial

Background Aortic dilatation is the main therapeutic target in patients with Marfan syndrome. Standard treatment with a β-blocker may not lower central pulse pressure - the major objective - because it does not do so in hypertension, unlike angiotensin-converting enzyme inhibitors and calcium-channel blockers. We therefore performed a prospective, randomised, double-blind, crossover trial to compare the effects of these three agents on large artery function and central aortic pressure in patients with Marfan syndrome. Methods and Results Eighteen patients had applanation tonometry, pulse wave analysis and echocardiography, before and after atenolol 75mg, perindopril 4mg and verapamil 240mg, each given for 4weeks, in a random order, with 2weeks between medications. Fourteen patients completed the study. Within-drug comparisons demonstrated that perindopril (-10·3mmHg, P=0·002), verapamil (-9·2mmHg, P=0·003) and atenolol (-7·1mmHg, P=0·01) all reduced central systolic pressure and brachial pressure; central changes were least, and peripheral changes greatest with atenolol but between-drug comparisons (analysis of covariance) were not significant. There was a trend for augmentation to be reduced by perindopril (-6·3%, P=0·05), verapamil (-5·5%, P=0·07) and atenolol (-3·2%, P=0·09). Only atenolol reduced heart rate (by 16%) and delayed expansion in the arch and abdominal aorta (by 8% and 11%) (P<0·001, P<0·01 and P<0·05, respectively, for between-drug comparisons). Conclusions Perindopril, verapamil and atenolol all reduced peripheral and central systolic pressure. As atenolol slowed heart rate and delayed aortic wave travel, β-blockade may have a continuing role in the treatment of patients with Marfan syndrome.