Rationale and design of a trial evaluating the effects of losartan vs. nebivolol vs. the association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations

Journal of Cardiovascular Medicine

Volumn 10, Issue 4, 2009, Pages 354-362

  Gambarin, Fabiana I ^a   Favalli, Valentina ^a   Serio, Alessandra ^a   Regazzi, Mario ^a   Pasotti, Michele ^a   Klersy, Catherine ^a   Dore, Roberto ^a   Mannarino, Savina ^a   Viganò, Mario ^a   Odero, Attilio ^a   Amato, Simona ^a   Tavazzi, Luigi ^a   Arbustini, Eloisa ^a  

^a FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

Author keywords

Aortic root dilation; Losartan; Marfan syndrome; Nebivolol

Indexed keywords

ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; LOSARTAN; NEBIVOLOL; TRANSFORMING GROWTH FACTOR BETA; ACTIN BINDING PROTEIN; ANGIOTENSIN RECEPTOR ANTAGONIST; BENZOPYRAN DERIVATIVE; ETHANOLAMINE DERIVATIVE; FIBRILLIN;

ADOLESCENT; ADULT; AORTA ANEURYSM; AORTA ROOT; ARTICLE; CHILD; CLINICAL ASSESSMENT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE COURSE; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; FBN1 GENE; FEMALE; GENE EXPRESSION; GENE MUTATION; HEART RATE; HUMAN; INFANT; MAJOR CLINICAL STUDY; MALE; MARFAN SYNDROME; PHARMACOGENETICS; PHARMACOGENOMICS; PHASE 3 CLINICAL TRIAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; TRANSCRIPTOMICS; UNSPECIFIED SIDE EFFECT; BLOOD; COMPARATIVE STUDY; GENETICS; LESIONS AND DEFECTS; METABOLISM; METHODOLOGY; MIDDLE AGED; MUTATION; PRESCHOOL CHILD; TIME; TREATMENT OUTCOME;

ADOLESCENT; ADRENERGIC BETA-ANTAGONISTS; ADULT; ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; AORTIC ANEURYSM; BENZOPYRANS; CHILD; CHILD, PRESCHOOL; DILATATION, PATHOLOGIC; DISEASE PROGRESSION; ETHANOLAMINES; FEMALE; HUMANS; INFANT; LOSARTAN; MALE; MARFAN SYNDROME; MICROFILAMENT PROTEINS; MIDDLE AGED; MUTATION; QUALITY OF LIFE; RESEARCH DESIGN; TIME FACTORS; TRANSFORMING GROWTH FACTOR BETA; TREATMENT OUTCOME; YOUNG ADULT;

EID: 66149129126     PISSN: 15582027     EISSN: None     Source Type: Journal    
DOI: 10.2459/JCM.0b013e3283232a45     Document Type: Article

References (68)

1. Dean JC. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet 2007; 15:724-733. (Pubitemid 46969881)
2. Groenink M, Lohuis TA, Tijssen JG, Naeff MS, Hennekam RC, van der Wall EE, Mulder BJ. Survival and complication free survival in Marfan's syndrome: implications of current guidelines. Heart 1999; 82:499-504. (Pubitemid 29475213)
3. Hamaguchi A, Kim S, Izumi Y, Zhan Y, Yamanaka S, Iwao H. Contribution of extracellular signal-regulated kinase to angiotensin II-induced transforming growth factor-beta1 expression in vascular smooth muscle cells. Hypertension 1999; 34:126-131. (Pubitemid 29325730)
4. Hao J, Wang B, Jones SC, Jassal DS, Dixon IM. Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol 2000; 279:H3020-H3030. (Pubitemid 32005893)
5. Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, et al. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 2001; 103:789-791. (Pubitemid 32163874)
6. el-Agroudy AE, Hassan NA, Foda MA, Ismail AM, el-Sawy EA, Mousa O, Ghoneim MA. Effect of angiotensin II receptor blocker on plasma levels of TGF-beta 1 and interstitial fibrosis in hypertensive kidney transplant patients. Am J Nephrol 2003; 23:300-306.
7. Ruiz-Ortega M, Ruperez M, Esteban V, Egido J. Molecular mechanisms of angiotensin II-induced vascular injury. Curr Hypertens Rep 2003; 5:73-79. (Pubitemid 38898935)
8. Campbell SE, Katwa LC. Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts. J Mol Cell Cardiol 1997; 29:1947-1958.
9. Huang W, Alhenc Gelas F, Osborne-Pellegrin MJ. Protection of the arterial internal elastic lamina by inhibition of the renin-angiotensin system in the rat. Circ Res 1998; 82:879-890. (Pubitemid 28234579)
10. Boffa JJ, Tharaux PL, Placier S, Ardaillou R, Dussaule JC, Chatziantoniou C. Angiotensin II activates collagen type I gene in the renal vasculature of transgenic mice during inhibition of nitric oxide synthesis: evidence for an endothelin-mediated mechanism. Circulation 1999; 100:1901-1908. (Pubitemid 29511144)
11. Verrecchia F, Mauviel A. Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol 2002; 118:211-215. (Pubitemid 34158472)
12. Massagué J, Chen YG. Controlling TGF-beta signaling. Genes Dev 2000; 14:627-644.
13. Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int 1997; 51:1376-1382. (Pubitemid 27239886)
14. Isogai Z, Ono RN, Ushiro S, Keene DR, Chen Y, Mazzieri R, et al. Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. J Biol Chem 2003; 278:2750-2757. (Pubitemid 36801356)
15. Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003; 33:407-411. (Pubitemid 36278859)
16. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2006; 312:117-121.
17. Chaudhry SS, Cain SA, Morgan A, Dallas SL, Shuttleworth CA, Kielty CM. Fibrillin-1 regulates the bioavailability of TGFbeta1. J Cell Biol 2007; 176:355-367.
18. Williams JA, Loeys BL, Nwakanma LU, Dietz HC, Spevak PJ, Patel ND, et al. Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease. Ann Thorac Surg 2007; 83:S757-S763.
19. Gómez-Garre D, Martín-Ventura JL, Granados R, Sancho T, Torres R, Ruano M, et al. Losartan improves resistance artery lesions and prevents CTGF and TGF-beta production in mild hypertensive patients. Kidney Int 2006; 69:1237-1244.
20. Rodrìguez-Vita J, Sànchez-Lòpez E, Esteban V, Rupérez M, Egido J, Ruiz-Ortega M. Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factor-beta-independent mechanism. Circulation 2005; 111:2509-2517.
21. Shin GT, Kim SJ, Ma KA, Kim HS, Kim D. ACE inhibitors attenuate expression of renal transforming growth factor-beta1 in humans. Am J Kidney Dis 2000; 36:894-902. (Pubitemid 30809912)
22. Fukuda N, Hu WY, Kubo A, Kishioka H, Satoh C, Soma M, et al. Angiotensin II upregulates transforming growth factor-beta type I receptor on rat vascular smooth muscle cells. Am J Hypertens 2000; 13:191-198. (Pubitemid 30125643)
23. Rupérez M, Lorenzo O, Blanco-Colio LM, Esteban V, Egido J, Ruiz-Ortega M. Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation 2003; 108:1499-1505. (Pubitemid 37176458)
24. Border WA, Noble NA. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension 1998; 318 (1 Pt 2):181-188. (Pubitemid 28124713)
25. Fakhouri F, Placier S, Ardaillou R, Dussaule JC, Chatziantoniou C. Angiotensin II activates collagen type I gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-beta. J Am Soc Nephrol 2001; 12:2701-2710. (Pubitemid 33115417)
26. Khalil A, Tullus K, Bakhiet M, Burman LG, Jaremko G, Brauner A. Angiotensin II type 1 receptor antagonist (losartan) down-regulates transforming growth factor-beta in experimental acute pyelonephritis. J Urol 2000; 164:186-191. (Pubitemid 30434298)
27. Erman A, Veksler S, Gafter U, Boner G, Wittenberg C, van Dijk DJ. Reninangiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat. J Renin Angiotensin Aldosterone Syst 2004; 5:146-151. (Pubitemid 39406724)
28. Campistol JM, Iňigo P, Jimenez W, Lario S, Clesca PH, Oppenheimer F, Rivera F. Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy. Kidney Int 1999; 56:714-719. (Pubitemid 29353172)
29. Cohn RD, van Erp C, Habashi JP, Soleimani AA, Klein EC, Lisi MT, et al. Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nat Med 2007; 13:204-210; Erratum in: Nat Med. 2007; 13:511.
30. Kaynar K, Ulusoy S, Ovali E, Vanizor B, Dikmen T, Gul S. TGF-beta and TNF-alpha producing effects of losartan and amlodipine on human mononuclear cell culture. Nephrology 2005; 10:478-482. (Pubitemid 41727272)
31. Yim HE, Kim MK, Bae IS, Kim JH, Choi BM, Yoo KH, et al. AT1 antagonist modulates activin-like kinase 5 and TGF-beta receptor II in the developing kidney. Pediatr Nephrol 2006; 21:1377-1388.
32. Sandor G, van Breemen C, Potts JE. A randomized double-blind study assessing the effects of losartan versus atenolol on pulse wave velocity and the biophysical properties of the aorta in patients with Marfan syndrome. Registered at ClinicalTrials.gov no. NCT00593710. http://www.clinicaltrials.gov/ ct2/show/NCT00593710?term=NCT00593710&rank=1.
33. Lacro RV, Dietz HC, Wruck LM, Bradley TJ, Colan SD, Devereux RB, 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; 154:624-631.
34. von Kodolitsch Y, Robinson PN. Marfan syndrome: an update of genetics, medical and surgical management. Heart 2007; 93:755-760. (Pubitemid 46808288)
35. Selamet Tierney ES, Feingold B, Printz BF, Park SC, Graham D, Kleinman CS, et al. Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome. J Pediatr 2007; 150:77-82. (Pubitemid 44940887)
36. 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; 114:303-308. (Pubitemid 44855907)
37. Ammash NM, Sundt TM, Connolly HM. Marfan syndrome - diagnosis and management. Curr Probl Cardiol 2008; 33:7-39.
38. Ahimastos AA, Aggarwal A, D'Orsa KM, Formosa MF, White AJ, Savarirayan R, et al. Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA 2007; 298:1539-1547. (Pubitemid 47529388)
39. 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; 95:1125-1127.
40. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med 2008; 358:2787-2795. (Pubitemid 351930853)
41. Sweetman CS, editor. Martindale: the complete drug reference. 33rd ed. London: Pharmaceutical Press; 2002.
42. Pauwels PJ, Gommeren W, Van Lommen G, Janssen PA, Leysen JE. The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockers. Mol Pharmacol 1988; 34:843-851. (Pubitemid 19014407)
43. Nuttall SL, Routledge HC, Kendall MJ. A comparison of the beta1- selectivity of three beta1-selective beta-blockers. J Clin Pharm Ther 2003; 28:179-186.
44. Ignarro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third-generation beta-blocker. Blood Press Suppl 2004; 1:2-16.
45. Ladage D, Brixius K, Hoyer H, Steingen C, Wesseling A, Malan D, et al. Mechanisms underlying nebivolol-induced endothelial nitric oxide synthase activation in human umbilical vein endothelial cells. Clin Exp Pharmacol Physiol 2006; 33:720-724. (Pubitemid 44060764)
46. Dessy C, Saliez J, Ghisdal P, Daneau G, Lobysheva II, Frérart F, et al. Endothelial β3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation β-blocker nebivolol. Circulation 2005; 112:1198-1205. (Pubitemid 41216127)
47. McEniery CM, Schmitt M, Qasem A, Webb DJ, Avolio AP, Wilkinson IB, Cockcroft JR. Nebivolol increases arterial distensibility in vivo. Hypertension 2004; 44:305-310. (Pubitemid 39167227)
48. Nollen GJ, Groenink M, Tijssen JGP, van der Wall EE, Mulder BJM. Aortic stiffness and diameter predict progressive aortic dilatation in patients with Marfan syndrome. Eur Heart J 2004; 25:1146-1152. (Pubitemid 38834072)
49. Bloom BS. Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther 1998; 20:671-681. (Pubitemid 28421488)
50. Van Bortel LM, Bulpitt CJ, Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am J Hypertens 2005; 18:1060-1066. (Pubitemid 41139904)
51. Hall PE, Kendall MJ, Smith SR. Beta blockers and fatigue. J Clin Hosp Pharm 1984; 9:283-291.
52. Moen MD, Wagstaff AJ. Nebivolol: a review of its use in the management of hypertension and chronic heart failure. Drugs 2006; 66:1389-1409. (Pubitemid 44246620)
53. Suzuki H, Tominaga T, Kumagai H, Saruta T. Effects of first-line antihypertensive agents on sexual function and sex hormones. J Hypertens Suppl 1988; 6:S649-S651. (Pubitemid 19067433)
54. Feleke E, Lyngstam O, Råstam L, Rydén L. Complaints of cold extremities among patients on antihypertensive treatment. Acta Med Scand 1983; 213:381-385.
55. Mangrella M, Rossi F, Fici F, Rossi F. Pharmacology of nebivolol. Pharmacol Res 1998; 38:419-431.
56. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30:473-483.
57. Guidotti M. Mathematical models for pharmacokinetics. Chapter 6. http://www.galenotech.org/farmcocin6.htm.
58. Roman MJ, Devereux RB, Kramer-Fox R, O'Loughlin J. Two dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 1989; 64:507-512. (Pubitemid 19214582)
59. Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet 2005; 44:797-814.
60. Veverka A, Nuzum DS, Jolly JL. Nebivolol: a third-generation betaadrenergic blocker. Ann Pharmacother 2006; 40:1353-1360.
61. Van Bortel LM, de Hoon JN, Kool MJ, Wijnen JA, Vertommen CI, Van Nueten LG. Pharmacological properties of nebivolol in man. Eur J Clin Pharmacol 1997; 51:379-384.
62. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 2007; 116:496-526. (Pubitemid 350116943)
63. Theken KN, Lee CR. Genetic variation in the cytochrome P450 epoxygenase pathway and cardiovascular disease risk. Pharmacogenomics 2007; 8:1369-1383.
64. Lazarevic AM, Nakatani S, Okita Y, Marinkovic J, Takeda Y, Hirooka K, et al. Determinants of rapid progression of aortic root dilatation and complications in Marfan syndrome. Int J Cardiol 2006; 106:177-182. (Pubitemid 41728935)
65. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996; 62:417-426. (Pubitemid 26131122)
66. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991; 352:337-339.
67. Arbustini E, Grasso M, Ansaldi S, Malattia C, Pilotto A, Porcu E, et al. Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies. Hum Mutat 2005; 26:494-508.
68. Pasotti M, Mannarino S, Serio A, Codazzi AC, Mancini L, Gambarin FI, et al. Evaluation of stiffness parameters based on e-tracking method in healthy young subjects [abstract]. Eur J Echocardiogr 2008; 9:S66.