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 ß-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 75 mg, perindopril 4 mg and verapamil 240 mg, each given for 4 weeks, in a random order, with 2 weeks between medications. Fourteen patients completed the study. Within-drug comparisons demonstrated that perindopril (-10·3 mmHg, P = 0·002), verapamil (-9·2 mmHg, P = 0·003) and atenolol (-7·1 mmHg, 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, ß-blockade may have a continuing role in the treatment of patients with Marfan syndrome.