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A systematic review of the pharmacological management of aortic root dilation in Marfan syndrome

Published online by Cambridge University Press:  19 October 2012

Varsha Thakur
Affiliation:
Division of Cardiology, The Hospital for Sick Children, Toronto, Canada
Kathryn N. Rankin
Affiliation:
Division of Cardiology, Stollery Children's Hospital, Edmonton, Canada Department of Pediatrics, University of Alberta, Edmonton, Canada
Lisa Hartling
Affiliation:
Department of Pediatrics, University of Alberta, Edmonton, Canada Alberta Research Centre for Health Evidence, University of Alberta, Edmonton, Canada
Andrew S. Mackie*
Affiliation:
Division of Cardiology, Stollery Children's Hospital, Edmonton, Canada Department of Pediatrics, University of Alberta, Edmonton, Canada
*
Correspondence to: Dr A. S. Mackie, MD, SM, Division of Cardiology, Stollery Children's Hospital, 8440-112th Street NW, Edmonton, AB, Canada T6G 2B7. Tel: +1 (780) 407 8361; Fax: +1 (780) 407 3954; E-mail: andrew.mackie@ualberta.ca

Abstract

Background

Marfan syndrome causes aortic dilation leading to dissection and death. This systematic review examined the use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers in the management of aortic dilation in this disease.

Methods

We searched four databases – Medline, EMBASE, Web of Science, and The Cochrane Central Register of Controlled Trials – two conference proceedings, references of retrieved articles, and a web-based trial registry. The primary outcome was mortality. The secondary outcomes were aortic dissection, need for elective surgical repair, change in aortic dilation, and adverse events. Two reviewers selected studies, abstracted data, and assessed study quality. Meta-analyses were not performed because of study heterogeneity.

Results

A total of 18 studies were included – 12 completed and six in progress. Of the completed studies, three before-and-after treatment, one prospective cohort, three retrospective cohorts, and two randomised control trials examined beta-blockers; one randomised and one non-randomised trial examined angiotensin-converting enzyme inhibitors; and one retrospective cohort study examined angiotensin II receptor blockers. Studies in progress are all randomised trials. Mortality was not impacted by drug therapy, although studies were underpowered with respect to this outcome. All drug classes were associated with a decrease in the rate of aortic dilation (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers >beta-blockers); none had an impact on other secondary outcomes.

Conclusions

On the basis of existing evidence, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers slow the progression of aortic dilation in Marfan syndrome. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may have more effect than beta-blockers; however, more methodologically rigorous studies currently in progress are needed to evaluate the impact of drug therapy on clinical outcomes.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012 

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References

1. Murdoch, JL, Walker, BA, Halpern, BL, Kuzma, JW, McKusick, VA. Life expectancy and causes of death in the Marfan syndrome. N Engl J Med 1972; 286: 804808.CrossRefGoogle ScholarPubMed
2. van Karnebeek, CD, Naeff, MS, Mulder, BJ, Hennekam, RC, Offringa, M. Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child 2001; 84: 129137.CrossRefGoogle ScholarPubMed
3. Roman, MJ, Rosen, SE, Kramer-Fox, R, Devereux, RB. Prognostic significance of the pattern of aortic root dilation in the Marfan syndrome. J Am Coll Cardiol 1993; 22: 14701476.CrossRefGoogle Scholar
4. Aburawi, EH, O'Sullivan, J. Relation of aortic root dilatation and age in Marfan's syndrome. Eur Heart J 2007; 28: 376379.CrossRefGoogle ScholarPubMed
5. Mukherjee, D, Eagle, KA. Aortic dissection – an update. Curr Probl Cardiol 2005; 30: 287325.CrossRefGoogle ScholarPubMed
6. Williams, A, Davies, S, Stuart, AG, Wilson, DG, Fraser, AG. Medical treatment of Marfan syndrome: a time for change. Heart 2008; 94: 414421.CrossRefGoogle Scholar
7. Gersony, DR, McClaughlin, MA, Jin, Z, Gersony, WM. The effect of beta-blocker therapy on clinical outcome in patients with Marfan's syndrome: a meta-analysis. Int J Cardiol 2007; 114: 303308.CrossRefGoogle ScholarPubMed
8. Higgins, JPT, Green, S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org Google Scholar
9. Stroup, DF, Berlin, JA, Morton, SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group. JAMA 2000; 283: 20082012.CrossRefGoogle ScholarPubMed
10. Ahimastos, AA, Aggarwal, A, D'Orsa, KM, et al. Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA 2007; 298: 15391547.CrossRefGoogle ScholarPubMed
11. Brooke, BS, Habashi, JP, Judge, DP, Patel, N, Loeys, B, Dietz, HC III. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med 2008; 358: 27872795.CrossRefGoogle ScholarPubMed
12. De Backer, J. The expanding cardiovascular phenotype of Marfan syndrome. Eur J Echocardiogr 2009; 10: 213215.CrossRefGoogle ScholarPubMed
13. Gambarin, FI, Favalli, V, Serio, A, et al. Rationale and design of a trial evaluating the effects of losartan versus Nebivolol versus the association of both on the progression of aortic root dilation in Marfan syndrome with fbn1 gene mutations. J Cardiovasc Med (Hagerstown) 2009; 10: 354362.CrossRefGoogle Scholar
14. Jondeau, G Multicenter, Randomised, Double Blind Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome, 2008; 2010. Retrieved May 2010 from http://www.Clinicaltrials.Gov/ct2/show/nct00763893?Term=marfan+syndrome+and+aortic+root+dilatation+and+beta-blockers+or+ace+inhibitors+or+angiotensin+receptor+blockers&rank=501 Google Scholar
15. Lacro, RV, Dietz, HC, Wruck, LM, et al. Rationale and design of a randomized clinical trial of beta-blocker therapy (atenolol) versus angiotensin ii receptor blocker therapy (losartan) in individuals with Marfan syndrome. Am Heart J 2007; 154: 624631.CrossRefGoogle ScholarPubMed
16. Ladouceur, M, Fermanian, C, Lupoglazoff, JM, et al. Effect of beta-blockade on ascending aortic dilatation in children with the Marfan syndrome. Am J Cardiol 2007; 99: 406409.CrossRefGoogle Scholar
17. Radonic, T, de Witte, P, Baars, MJ, Zwinderman, AH, Mulder, BJ, Groenink, M. Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled compare trial. Trials 2010; 11: 3.CrossRefGoogle ScholarPubMed
18. Reed, CM, Alpert, BS. Assessment of ventricular performance after chronic beta-adrenergic blockade in the Marfan syndrome. Am J Cardiol 1992; 70: 541542.CrossRefGoogle ScholarPubMed
19. Reed, CM, Fox, ME, Alpert, BS. Aortic biomechanical properties in pediatric patients with the Marfan syndrome, and the effects of atenolol. Am J Cardiol 1993; 71: 606608.CrossRefGoogle Scholar
20. Rios, AS, Silber, EN, Bavishi, N, et al. Effect of long-term beta-blockade on aortic root compliance in patients with Marfan syndrome. Am Heart J 1999; 137: 1 0571061.CrossRefGoogle ScholarPubMed
21. Rossi-Foulkes, R, Roman, MJ, Rosen, SE, et al. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol 1999; 83: 13641368.CrossRefGoogle ScholarPubMed
22. Salim, MA, Alpert, BS, Ward, JC, Pyeritz, RE. Effect of beta-adrenergic blockade on aortic root rate of dilation in the Marfan syndrome. Am J Cardiol 1994; 74: 629633.CrossRefGoogle ScholarPubMed
23. Selamet Tierney, ES, Feingold, B, Printz, BF, et al. Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome. J Pediatr 2007; 150: 7782.CrossRefGoogle Scholar
24. Shores, J, Berger, KR, Murphy, EA, Pyeritz, RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med 1994; 330: 13351341.CrossRefGoogle ScholarPubMed
25. Tahernia, AC. Cardiovascular anomalies in Marfan's syndrome: the role of echocardiography and beta-blockers. South Med J 1993; 86: 305310.CrossRefGoogle ScholarPubMed
26. Wu, M. Randomized, Open-Label, Active Control Trial to Evaluate the Effect of LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome, 2008; 2010. http://www.Clinicaltrials.Gov/ct2/show/nct00651235?Term=marfan+syndrome+and+aortic+root+dilatation+and+beta-blockers+or+ace+inhibitors+or+angiotensin+receptor+blockers&rank=240a.Google Scholar
27. Yetman, AT, Bornemeier, RA, McCrindle, BW. Usefulness of enalapril versus propranolol or atenolol for prevention of aortic dilation in patients with the Marfan syndrome. Am J Cardiol 2005; 95: 11251127.CrossRefGoogle ScholarPubMed
28. Raoux, F. Effect of beta-blockade on ascending aortic dilatation in children with Marfan syndrome. MT Cardio 2007; 3: 362364.Google Scholar
29. Engelfriet, P, Mulder, B. Is there benefit of beta-blocking agents in the treatment of patients with the Marfan syndrome? Int J Cardiol 2007; 114: 300302.CrossRefGoogle ScholarPubMed
30. Lu, H, Rateri, DL, Cassis, LA, Daugherty, A. The role of the renin–angiotensin system in aortic aneurysmal diseases. Curr Hypertens Rep 2008; 10: 99106.CrossRefGoogle ScholarPubMed
31. Habashi, JP, Judge, DP, Holm, TM, et al. Losartan, an at1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2006; 312: 117121.CrossRefGoogle Scholar
32. Gott, VL, Greene, PS, Alejo, DE, et al. Replacement of the aortic root in patients with Marfan's syndrome. N Engl J Med 1999; 340: 13071313.CrossRefGoogle ScholarPubMed
33. Davies, RR, Gallo, A, Coady, MA, et al. Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms. Ann Thorac Surg 2006; 81: 169177.CrossRefGoogle ScholarPubMed
34. Davies, RR, Goldstein, LJ, Coady, MA, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size. Ann Thorac Surg 2002; 73: 1727; discussion 27-18.CrossRefGoogle Scholar
35. Hwa, J, Richards, JG, Huang, H, et al. The natural history of aortic dilatation in Marfan syndrome. Med J Aust 1993; 158: 558562.Google ScholarPubMed
36. Pyeritz, RE. Marfan syndrome: 30 years of research equals 30 years of additional life expectancy. Heart 2009; 95: 173175.CrossRefGoogle ScholarPubMed
37. Pyeritz, RE, McKusick, VA. The Marfan syndrome: diagnosis and management. N Engl J Med 1979; 300: 772777.CrossRefGoogle ScholarPubMed
38. Beighton, P, de Paepe, A, Danks, D, et al. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet 1988; 29: 581594.CrossRefGoogle Scholar
39. De Paepe, A, Devereux, RB, Dietz, HC, Hennekam, RC, Pyeritz, RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996; 62: 417426.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
40. Loeys, BL, Dietz, HC, Braverman, AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010; 47: 476485.CrossRefGoogle ScholarPubMed
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