Simvastatin as a treatment for pulmonary hypertension trial

American Journal of Respiratory and Critical Care Medicine

Volumn 181, Issue 10, 2010, Pages 1106-1113

  Wilkins, Martin R ^a   Ali, Omar ^a   Bradlow, William ^a,b   Wharton, John ^a   Taegtmeyer, Anne ^a   Rhodes, Christopher J ^a   Ghofrani, Hossein A ^c   Howard, Luke ^a   Nihoyannopoulos, Petros ^a   Mohiaddin, Raad H ^b   Gibbs, J Simon R ^a,b  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

^b NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^c UNIVERSITY HOSPITAL GIESSEN   (Germany)

Author keywords

Hypertension; Hypertrophy; MRI; Pulmonary; Simvastatin

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; BONE MORPHOGENETIC PROTEIN 15; CYTOKINE; NITRIC OXIDE; SIMVASTATIN; ANTIHYPERTENSIVE AGENT; BRAIN NATRIURETIC PEPTIDE; PEPTIDE FRAGMENT; PRO BRAIN NATRIURETIC PEPTIDE (1 76); PRO-BRAIN NATRIURETIC PEPTIDE (1-76);

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXERCISE; FEMALE; HEART FUNCTION; HEART INDEX; HEART RIGHT VENTRICLE; HEART VOLUME; HUMAN; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PULMONARY HYPERTENSION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE; BLOOD; ECHOGRAPHY; HEART RIGHT VENTRICLE HYPERTROPHY; MIDDLE AGED; PATHOLOGY;

ADULT; AGED; ANTIHYPERTENSIVE AGENTS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; MALE; MIDDLE AGED; NATRIURETIC PEPTIDE, BRAIN; PEPTIDE FRAGMENTS; SIMVASTATIN; YOUNG ADULT;

EID: 77953273837     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.2009111-699OC     Document Type: Article

References (40)

1. Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 2009;54:S10-S19.
2. NationalPulmonary Hypertension Centres of the UK and Ireland. Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax 2008;63:ii1-ii41.
3. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008;14:37-44.
4. Girgis RE, Li D, Zhan X, Garcia JG, Tuder RM, Hassoun PM, Johns RA. Attenuation of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Heart Circ Physiol 2003;285:H938-H945. (Pubitemid 37048146)
5. Guerard P, Rakotoniaina Z, Goirand F, Rochette L, Dumas M, Lirussi F, Bardou M. The HMG-CoA reductase inhibitor, pravastatin, prevents the development of monocrotaline-induced pulmonary hypertension in the rat through reduction of endothelial cell apoptosis and overexpression of eNOS. Naunyn Schmiedebergs Arch Pharmacol 2006;373:401-414. (Pubitemid 44401411)
6. Laudi S, Trump S, Schmitz V, West J, McMurtry IF, Mutlak H, Christians U, Weimann J, Kaisers U, Steudel W. Serotonin transporter protein in pulmonary hypertensive rats treated with atorvastatin. Am J Physiol Lung Cell Mol Physiol 2007;293:L630-L638. (Pubitemid 47358825)
7. Murata T, Kinoshita K, Hori M, Kuwahara M, Tsubone H, Karaki H, Ozaki H. Statin protects endothelial nitric oxide synthase activity in hypoxia-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol 2005;25:2335-2342. (Pubitemid 41552651)
8. Nishimura T, Faul JL, Berry GJ, Vaszar LT, Qiu D, Pearl RG, Kao PN. Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. Am J Respir Crit Care Med 2002;166:1403-1408. (Pubitemid 35292709)
9. Rakotoniaina Z, Guerard P, Lirussi F, Goirand F, Rochette L, Dumas M, Bardou M. The protective effect of HMG-CoA reductase inhibitors against monocrotaline-induced pulmonary hypertension in the rat might not be a class effect: comparison of pravastatin and atorvastatin. Naunyn Schmiedebergs Arch Pharmacol 2006;374:195-206. (Pubitemid 44819252)
10. Satoh K, Fukumoto Y, Nakano M, Sugimura K, Nawata J, Demachi J, Karibe A, Kagaya Y, Ishii N, Sugamura K, et al. Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1. Cardiovasc Res 2009;81:226-234.
11. Satoh M, Satoh A. 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors and phosphodiesterase type V inhibitors attenuate right ventricular pressure and remodeling in a rat model of pulmonary hypertension. J Pharm Pharm Sci 2008;11:118s-130s.
12. Sun X, Ku DD. Rosuvastatin provides pleiotropic protection against pulmonary hypertension, right ventricular hypertrophy, and coronary endothelial dysfunction in rats. Am J Physiol Heart Circ Physiol 2008;294:H801-H809. (Pubitemid 351253291)
13. Nishimura T, Vaszar LT, Faul JL, Zhao G, Berry GJ, Shi L, Qiu D, Benson G, Pearl RG, Kao PN. Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells. Circulation 2003;108:1640-1645. (Pubitemid 37187793)
14. Girgis RE, Mozammel S, Champion HC, Li D, Peng X, Shimoda L, Tuder RM, Johns RA, Hassoun PM. Regression of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Lung Cell Mol Physiol 2007;292:L1105-L1110. (Pubitemid 47084854)
15. McMurtry MS, Bonnet S, Michelakis ED, Bonnet S, Haromy A, Archer SL. Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: the rapamcyin-atorvastatin-simvastatin study. Am J Physiol Lung Cell Mol Physiol 2007;293:L933-L940. (Pubitemid 47572241)
16. Zhao L, Sebkhi A, Ali O, Wojciak-Stothard B, Mamanova L, Yang Q, Wharton J, Wilkins MR. Simvastatin and sildenafil combine to attenuate pulmonary hypertension. Eur Respir J 2009;34:948-957.
17. Kao PN. Simvastatin treatment of pulmonary hypertension: an observational case series. Chest 2005;127:1446-1452. (Pubitemid 46224314)
18. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991;115:343-349.
19. Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 1994;89:1733-1744.
20. van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 2007;28:1250-1257. (Pubitemid 47343830)
21. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006;114:1883-1891.
22. Nickel N, Kempf T, Tapken H, Tongers J, Laenger F, Lehmann U, Golpon H, Olsson K, Wilkins MR, Gibbs JS, et al. Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2008;178:534-541.
23. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009;119:2250-2294.
24. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;34:1219-1263.
25. Maceira AM, Prasad SK, Khan M, Pennell DJ. Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance. Eur Heart J 2006;27:2879-2888. (Pubitemid 44871471)
26. Chai P, Mohiaddin R. How we perform cardiovascular magnetic resonance flow assessment using phase-contrast velocity mapping. J Cardiovasc Magn Reson 2005;7:705-716. (Pubitemid 41176838)
27. Ryan T, Petrovic O, Dillon JC, Feigenbaum H, Conley MJ, Armstrong WF. An echocardiographic index for separation of right ventricular volume and pressure overload. J Am Coll Cardiol 1985;5:918-927.
28. Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ, Seward SB. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr 1996;9:838-847.
29. Khan SQ, Ng K, Dhillon O, Kelly D, Quinn P, Squire IB, Davies JE, Ng LL. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J 2009;30:1057-1065.
30. Omland T, Persson A, Ng L, O'Brien R, Karlsson T, Herlitz J, Hartford M, Caidahl K. N-terminal pro-B-type natriuretic peptide and longterm mortality in acute coronary syndromes. Circulation 2002;106:2913-2918. (Pubitemid 35424741)
31. Connelly L, Madhani M, Hobbs AJ. Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a proinflammatory role for eNOS-derived no in vivo. J Biol Chem 2005;280:10040-10046. (Pubitemid 40395855)
32. Sullivan LM. Repeated measures. Circulation 2008;117:1238-1243.
33. Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, Drexler H, Johnston N, Wallentin L, Wollert KC. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 2007;53:284-291. (Pubitemid 46338273)
34. Liu J, Shen Q, Wu Y. Simvastatin prevents cardiac hypertrophy in vitro and in vivo via JAK/STAT pathway. Life Sci 2008;82:991-996.
35. Takemoto M, Node K, Nakagami H, Liao Y, Grimm M, Takemoto Y, Kitakaze M, Liao JK. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001;108:1429-1437. (Pubitemid 33091980)
36. Wu L, Zhao L, Zheng Q, Shang F, Wang X, Wang L, Lang B. Simvastatin attenuates hypertrophic responses induced by cardiotrophin-1 via JAK-STAT pathway in cultured cardiomyocytes. Mol Cell Biochem 2006;284:65-71. (Pubitemid 44404411)
37. McLaughlin VV, Badesch DB, Delcroix M, Fleming TR, Gaine SP, Galie N, Gibbs JS, Kim NH, Oudiz RJ, Peacock A, et al. End points and clinical trial design in pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:S97-S107.
38. Nissen SE. High-dose statins in acute coronary syndromes: not just lipid levels. JAMA 2004;292:1365-1367. (Pubitemid 39223231)
39. Wilkins MR, Paul GA, Strange JW, Tunariu N, Gin-Sing W, Banya WA, Westwood MA, Stefanidis A, Ng LL, Pennell DJ, et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med 2005;171:1292-1297. (Pubitemid 40740738)
40. Dingemanse J, Schaarschmidt D, van Giersbergen PL. Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet 2003;42:293-301. (Pubitemid 36308067)