title: Effects of atenolol, perindopril and verapamil on haemodynamic and vascular function in Marfan syndrome - a randomised, double-blind, crossover trial.
abstract: 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.
  
  
  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, β-blockade may have a continuing role in the treatment of patients with Marfan syndrome.
authors.affiliation: Wales Heart Research Institute, Cardiff University, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Damien
authors.initials: D
authors.lastname: Kenny
authors.forename: Dirk
authors.initials: D
authors.lastname: Wilson
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fagenello
authors.forename: Martyn
authors.initials: M
authors.lastname: Nelson
authors.forename: Frank
authors.initials: F
authors.lastname: Dunstan
authors.forename: John
authors.initials: J
authors.lastname: Cockcroft
authors.forename: Graham
authors.initials: G
authors.lastname: Stuart
authors.forename: Alan G
authors.initials: AG
authors.lastname: Fraser
mesh_terms: D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D020913:Perindopril / Q000494:pharmacology*; D011446:Prospective Studies; D014700:Verapamil / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D001262:Atenolol; D014700:Verapamil; D020913:Perindopril