Expert opinion on available options treating pulmonary arterial hypertension

Expert Opinion on Pharmacotherapy

Volumn 8, Issue 14, 2007, Pages 2247-2265

  Naeije, Robert ^a   Huez, Sandrine ^a  

^a ERASME HOSPITAL   (Belgium)

Author keywords

Endothelin receptor antagonist; Phosphodiesterase 5 inhibitor; Prostacyclin; Pulmonary arterial hypertension; Septostomy; Transplantation

Indexed keywords

AMBRISENTAN; ANTICOAGULANT AGENT; BERAPROST; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; COUMARIN DERIVATIVE; DILTIAZEM; DIURETIC AGENT; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; FASUDIL; FUROSEMIDE; ILOPROST; INOTROPIC AGENT; NIFEDIPINE; PHOSPHODIESTERASE III INHIBITOR; PHOSPHODIESTERASE IV INHIBITOR; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; RHO KINASE INHIBITOR; SILDENAFIL; SITAXSENTAN; TADALAFIL; UNINDEXED DRUG; UNIPROST; VASOACTIVE INTESTINAL POLYPEPTIDE; VASODILATOR AGENT;

ABDOMINAL CRAMP; BIRTH CONTROL; CLINICAL PROTOCOL; CLINICAL TRIAL; COUGHING; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG METABOLISM; DRUG WITHDRAWAL; DYSPEPSIA; ERYTHEMA; EXERCISE; FLUSHING; HEART TRANSPLANTATION; HEMODYNAMICS; HUMAN; HYPOTENSION; HYPOXIA; IDIOPATHIC DISEASE; JAW DISEASE; LEG PAIN; LIFE EXPECTANCY; LIVER TOXICITY; LUNG TRANSPLANTATION; MONOTHERAPY; MYALGIA; NAUSEA; NONHUMAN; NOSE CONGESTION; PAIN; PERIPHERAL EDEMA; PREGNANCY; PULMONARY HYPERTENSION; REVIEW; SIDE EFFECT; STEM CELL TRANSPLANTATION; SURVIVAL; SWELLING; VISUAL DISORDER;

ANTIHYPERTENSIVE AGENTS; CALCIUM CHANNEL BLOCKERS; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; HUMANS; HYPERTENSION, PULMONARY; VASODILATOR AGENTS;

EID: 35548959182     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.8.14.2247     Document Type: Review

References (149)

1. FARBER HW, LOSCALZO J: Pulmonary arterial hypertension. N. Engl. J. Med. (2004) 351:1655-1665.
2. HUMBERT M, SITBON O, SIMONNEAU G: Treatment of pulmonary arterial hypertension. N. Engl. J Med. (2004) 351:1425-1436.
3. MCLAUGHLIN V, PRESBERG KW, DOYLE RL et al.: Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest (2004) 126:S78-S92.
4. PROVENCHER S, SITBON O, HUMBERT M, CABROL S, JAIS X, SIMONNEAU G: Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur. Heart J. (2006) 27:589-595.
5. SIMONNEAU G, GALIE N, RUBIN LJ et al.: Clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. (2004) 43(12 Suppl. S):S5-S12.
6. HUMBERT M, SITBON O, CHAOUAT A et al.: Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. (2006) 173:1023-1030.
7. ABENHAIM L, MORIDE Y, BRENOT F et al.: Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International primary pulmonary hypertension study group. N Engl. J. Med. (1996) 335:609-616.
8. BARST RJ, MCGOON M, TORBICKI A et al.: Diagnosis and differential assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2004) 43(12 Suppl.):S40-S47.
9. NAEIJE R, VACHIERY JL: Medical therapy of pulmonary hypertension: conventional therapies. Clin. Chest Med. (2001) 22:517-528.
10. MERELES D, EHLKEN N, KREUSCHER S et al.: Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation (2006) 114:1482-1489.
11. HOEPER MM, LEE SH, VOSWINCKEL R et al.: Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J. Am. Coll. Cardiol. (2006) 48:2546-2552.
12. BONNIN M, MERCIER FJ, SITBON O et al.: Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology (2005) 102: 1133-1137.
13. OAKLEY C, SOMMERVILLE J: Oral contraceptives and pulmonary vascular disease. Lancet (1968) I:890-891.
14. NAEIJE R: Preflight medical screening of patients. Eur Respir. J. (2000) 16:197-199.
15. SANDOVAL J, AGUIRRE JS, PULIDO T et al.: Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am. J. Respir. Crit. Care Med. (2001) 164:1682-1687.
16. KUEHNE T, YILMAZ S, STEENDIJK P et al.: Magnetic resonance imaging analysis of right ventricular pressure-volume loops: in vivo validation and clinical application in patients with pulmonary hypertension. Circulation (2004) 110:2010-2016.
17. PROVENCHER S, HERVÉ P, JAIS X et al.: Deleterious effects of β-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology (2006) 130:120-126.
18. KERBAUL F, RONDELET B, MOTTE S et al.: Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure. Crit. Care Med. (2004) 32:1035-1040.
19. RICH S, KAUFMANN E, LEVY PS: The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N. Engl. J. Med. (1992) 327:76-81.
20. RICH S, SEIDLITZ M, DODIN E et al.: The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest (1998) 114:787-792.
21. WAGENVOORT CA, WAGENVOORT N: Primary pulmonary hypertension: a pathologic study of the lung vessels. Circulation (1970) 42:1163-1184.
22. FUSTER V, STEELE PM, EDWARDS WD et al.: Primary pulmonary hypertension: natural history and importance of thrombosis. Circulation (1984) 70:580-587.
23. HYERS TM: Venous thromboembolism. Am. J. Respir. Crit. Care Med. (1999) 159:1-14.
24. RAFFY O, AZARIAN R, BRENOT F et al.: Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension. Circulation (1996) 93:484-488.
25. SITBON O, HUMBERT M, JAIS X et al.: Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation (2005) 111:3105-3111.
26. MATHE AA, HEDQUIST P, STRANDBERG K, LESLIE CA: Aspects of prostaglandin function in the lung. N. Engl. J. Med. (1977) 296:850-855, 910-914.
27. LOCK JE, OLLEY PM, COCCEANI F, SWYER PR, ROWE RD: Use of prostacyclin in persistent fetal circulation. Lancet (1979) I:1343.
28. 1 for severe idiopathic pulmonary artery hypertension. Lancet (1980) I: 1083.
29. RUBIN LJ, GROVES BM, REEVES JT, FROSOLONO M, HANDEL F, CATO AE: Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation (1982) 66:334-338.
30. BLUMBERG FC, LORENZ C, WOLF K, SANDNER P, RIEGGER GA, PFEIFER M: Increased pulmonary prostacyclin synthesis in rats with chronic pulmonary hypertension. Cardiovasc. Res. (2002) 55:171-177.
31. ABE Y, TATSUMI K, SUGITO K, IKEDA Y, KIMURA H, KURIYAMA T: Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary hypertension. J. Cardiovasc. Pharmacol. (2001) 37:239-251.
32. SCHERMULY RT, YILMAZ H, GHOFRANI HA et al.: Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension. Am. J. Respir. Crit. Care Med. (2005) 172:358-363.
33. TUDER RM, COOL CD, GERACI NW et al.: Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am. J. Respir. Crit. Care Med. (1999) 159:1925-1932.
34. CHRISTMAN BW, MCPHERSON CD, NEWMAN JH et al.: An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N. Engl. J. Med. (1992) 327:70-75.
35. HIGENBOTTAM TW, WHEELDON D, WELLS FC, WALLWORK J: Long-term treatment pf primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Lancet (1984) I:1046-1047.
36. JONES KD, HIGENBOTTAM TW, WALLWORK J: Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin). Br. Heart J. (1987) 57:270-278.
37. HIGENBOTTAM TW, SPIEGELHALTER D, SCOTT JP et al.: Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for sevee pulmonary hypertension. Br. Heart J. (1993) 70:366-370.
38. RUBIN LJ, MENDOZA J, HOOD M et al.: Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann. Intern. Med. (1990) 112:485-491.
39. BARST RJ, RUBIN LJ, MCGOON MD, CALDWELL EJ, LONG WA, LEVY PS: Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin Ann. Intern. Med. (1994) 121:409-415.
40. BARST, RJ, RUBIN LJ, LONG WA et al.: A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N. Engl. J. Med. (1996) 334:296-301.
41. SHAPIRO SM, OUDIZ RJ, CAO T et al.: Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J. Am. Coll. Cardiol. (1997) 30:343-349.
42. BADESCH DR, TAPSON VF, MCGOON M et al.: Continuous intravenous epoprostenol for pulonary hypertension due to the scleroderma spectrum of disease. Ann. Intern. Med. (2000) 132:425-434.
43. ROSENZWEIG EB, KERSTEIN D, BARST RJ: Long-term prostacylin for pulmonary hypertension and associated congenital heart defects. Circulation (1999) 14:1858-1865.
44. KUO PC, PLOTKIN JS, HOWELL CD, BARTLETT ST, RUBIN LJ: Continuous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation (1997) 63:604-606.
45. NUNES H, HUMBERT M, SITBON O et al.: Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. (2003) 167:1433-1439.
46. ROBBINS IM, CHRISTMAN BW, NEWMAN JH, MATLOCK R, LOYD JE: A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension. Chest (1998) 114:1269-1275.
47. SITBON O, HUMBERT M, NUNES H et al.: Long-term intravenous epoprostenol in primary pulmonary hypertension. Prognostic factors and survival. J. Am. Coll. Cardiol. (2002) 40:780-788.
48. MCLAUGHLIN VV, SHILLINGTON A, RICH S: Survival in primary pulmonary hypertension. Circulation (2002) 106:1477-1482.
49. RICH S, MCLAUGHLIN V: The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J. Am. Coll. Cardiol. (1999) 34:1184-1187.
50. PALMERSM, ROBINSON LJ, WANG A, GOSSAGE JR, BASHORE T, TAPSON VE: Massive pulmonary edema and death after prostacyclin infusion in a patient with veno-occlusive disease. Chest (1998) 113:237-240.
51. HUMBERT M, MAITRE S, CAPRON F, RAIN B, MUSSET D, SIMONNEAU G: Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary capillary hemangiomatosis. Am. J. Respir. Crit. Care Med. (1998) 157:1681-1685.
52. VACHIERY JL, NAEIJE R: Treprostinil for pulmonary hypertension. Expert Rev. Cardiovasc. Ther. (2004) 2:183-189.
53. SIMONNEAU G, BARST RJ, GALIÉ, N et al.: Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. (2002) 162:800-804.
54. BARST RJ, GALIE N, NAEIJE R et al.: Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur. Respir. J. (2006) 28:1195-1203.
55. LANG I, GOMEZ-SANCHEZ M, KNEUSSL M et al.: Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest (2006) 129:1-8.
56. VACHIERY JL, HILL N, ZWICKE D, BARST R, BLACKBURN S, NAEIJE R: Transitioning from i.v. epoprostenol to subcutaneous treprostinil in pulmonary arterial hypertension. Chest (2002) 121:1561-12565.
57. GOMBERG-MAITLAND M, TAPSON VF, BENZA RL et al.: Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am. J. Respir. Crit. Care Med. (2005) 172:1586-1589.
58. CHANNICK RN, OLSCHEWSKI H, SEEGER W, STAUB T, VOSWINCKLE R, RUBIN LJ: Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2006) 48:433-1437.
59. OLSCHEWSKI H, SIMONNEAU G, GALIÉ N et al.: Inhaled iloprost is an effective treatment for severe pulmonary hypertension. A double-blind, placebo-controlled, multicenter study. N. Engl. J. Med. (2002) 347:322-329.
60. HOEPER MM, SCHWARZE M, EHLERDING S et al.: Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N. Engl. J. Med. (2000) 342:1866-1870.
61. OPITZ CF, WENSEL R, WINKLER J et al.: Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur. Heart J. (2005) 26:1895-1902.
62. HOEPER MM, SPIEKERKOETTER E, WESTERKAMP V, GATZKE R, FABEL H: Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension. Eur. Respir J. (2002) 20:339-343.
63. GALIÉ N, HUMBERT M, VACHIÉRY JL et al.: Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2002) 39:1496-1502.
64. BARST RJ, MCGOON M, MCLAUGHLIN V et al.: Beraprost study group. Beraprost therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2003) 41:2119-2125.
65. BERMAN ROSENZWEIG E, SCHMITT KA, GAROFANO R, BARST RJ: Identical twins with primary pulmonary hypertension: beraprost vs epoprostenol. Chest (2004) 125:1157-1160.
66. MOTTE S, NAEIJE R, MCENTEE K: Endothelin receptor antagonists. Pharmacol. Then. (2006) 110:386-414.
67. GIAID A, YANISAGAWA M, LANGLEBEN D et al.: Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl. J. Med. (1993) 328:1732-1739.
68. RONDELET B, KERBAUL F, MOTTE S et al.: Bosentan for the prevention of overcirculation-induced experimental pulmonary arterial hypertension. Circulation (2003) 107:1329-1335.
69. BLACK SM, MATA-GREENWOOD E, DETTMAN RW et al.: Emergence of smooth muscle cell endothelin B-mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow. Circulation (2003) 108:1646-1654.
70. NISHIDA M, ESHIRO K, OKADA Y, TAKAOKA M, MATSUMURA Y: Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension. J. Cardiovasc. Pharmacol. (2004) 44:187-191.
71. IVY DD, YANAGISAWA M, GARIEPY CE, GEBB SA, COLVIN KL, MCMURTRY IF: Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) 282:L703-L712.
72. CHEN SJ, CHEN IF, MENG QC, DURAND J, DI CARLO VS, OPARIL S: Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J. Appl. Physiol. (1995) 79:2122-2131.
73. DICARLOVS, CHEN SJ, MENG QC et al.: ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat. Am. J. Physiol. (1995) 269:L690-L697.
74. JASMIN JF, LUCAS M, CERNACEK P, DUPUIS J: Effectiveness of a nonselective ET(A/B) and a selective ET(A) antagonist in rats with monocrotaline-induced pulmonary hypertension. Circulation (2001) 103:314-318.
75. RONDELET B, KERBAUL F, VAN BENEDEN R et al.: Sitaxsentan for the prevention of experimental shunt-induced pulmonary hypertension in piglets. Ped. Res. (2007) 61:284-288.
76. CLOZEL M, BREU V, GRAY GA et al.: Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J. Pharmacol. Exp. Ther. (1994) 270:228-235.
77. WEBERC, SCHMITT R, BIRNBOECK H et al.: Pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist bosentan in healthy subjects. Clin. Pharmacol. Ther. (1996) 60:124-137.
78. CHANNICK RN, SIMONNEAU G, SITBON O et al.: Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study. Lancet (2001) 358:1119-1123.
79. RUBIN LJ, BADESCH RM, BARST R et al.: Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. (2002) 346:896-903.
80. GALIEN, HINDERLITER AL, TORBICKI A et al.: Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2003) 41:1380-1386.
81. SITBON O, BADESCH DB, CHANNICK RN et al.: Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest (2003) 124:247-254.
82. MCLAUGHLIN VV, SITBON O, BADESCH DB et al.: Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J. (2005) 25:244-249.
83. SITBON O, MCLAUGHLIN VV, BADESCH DB et al.: Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax (2005) 60:1025-1230.
84. PROVENCHERS, SITBON O, HUMBERT M, CABROL S, JAIS X, SIMONNEAU G: Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension Eur. Heart J. (2006) 27:589-595.
85. SITBON O, GRESSIN V, SPEICH R et al.: Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. (2004) 170:1212-1217.
86. HOEPER MM, HALANK M, MARX C et al.: Bosentan therapy for portopulmonary hypertension. Eur. Respir. J. (2005) 25:502-508.
87. GALIEN, BEGHETTI M, GATZOULIS MA et al.: Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation (2006) 114:48-54.
88. ROSENZWEIG EB, IVY DD, WIDLITZ A et al.: Effects of long-term bosentan in children with pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2005) 46:697-704.
89. FATTINGER K, FUNK C, PANTZE M et al.: The endothelin receptor antagonist bosentan inhibits the canalicular bile salt export pulmp: a potential mechanism for hepatic adverse reactions. Clin. Pharmacol. Ther. (2001) 69:223-231.
90. HUMBERT M, SEGAL ES, KIELY DG, CARLSEN J, SCHWIERIN B, HOEPER MM: Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur. Respir. J. (2007) 30:338-344.
91. MODESTI PA, VANNI S, MORABITO M et al.: Role of endothelin-1 in exposure to high altitude: acute mountain sickness and endothelin-1 (ACME-1) study. Circulation (2006) 114:1410-1416.
92. HUMBERT M, BARST RJ, ROBBINS IM et al.: Combination of bosentan with epoprostenol in pulmonary arterial hypertension. Eur. Respir. J. (2004) 24:353-359.
93. HOEPER MM, MARKEVYCH I, SPIEKERKOETTER E, WELTE T, NIEDERMEYER J: Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur. Respir. J. (2005) 26:858-863.
94. MATHAI SC, GIRGIS RE, FISHER MR et al.: Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur. Respir. J. (2007) 29:469-475.
95. BARST RJ: Sitaxsentan: a selective endothelin-A receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin. Pharmacother. (2007) 8:95-109.
96. BARST RJ, LANGLEBEN D, FROST A et al.: Sitaxsentan therapy for pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. (2005) 169:441-447.
97. BARST RJ, LANGLEBEN D, BADESCH D et al.: Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J. Am. Coll. Cardiol. (2006) 47:2049-2056,
98. PULIDO T, KURZINA M, SOUZA R, RAMIREZ A, SANDOVAL J: Sitaxsentan 100 mg proves more effective than sitaxsentan 50 mg in patients with pulmonary arterial hypertension. Proc. Am. Thorac. Soc. (2006) 3:A417.
99. BENZA RL, FROST A, GIRGIS D, LENGLEBEN D, LAWRENCE EC, NAEIJE R: Chronic treatment of pulmonary arterial hypertension (PAH) with sitaxsentan and bosentan. Proc. Am. Thorac. Soc. (2006) 3:A729.
100. BENZA RL, MEHTA S, KEOGH A et al.: Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan. J. Heart Lung Transplant. (2007) 26:63-69.
101. BILLMAN GE: Ambrisentan (Myogen). Curr. Opin. Investig. Drugs (2002) 3:1483-1486.
102. GALIE N, BADESCH D, OUDIZ R et al.: Ambrisentan therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2005) 46:529-535.
103. OUDIZ RJ, TORRES F, FROST AE et al.: ARIES-1: a placebo-controlled efficacy and safety study of administration of ambrisentan in patients with pulmonary arterial hypertension. Chest (2006) 130S:S121.
104. OLSCHEWSKI H, GALIÉ N, GHOFRANI HA et al.: Ambrisentan improves exercise capacity and time to clinical worsening in patients with pulmonary arterial hypertension: results of the ARIES-2 study. Proc. Am. Thorac. Soc. (2006) 3:A728.
105. SEBKHI A, STRANGE JW, PHILIPS SC, WHARTON J, WILKINS M: Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation (2003) 107:3230-3235.
106. SCHERMULY RT, KREISSELMEIER KP, GHOFRANI HA et al.: Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am. J. Respir. Crit. Care Med. (2004) 169:39-45.
107. RONDELET B, KERBAUL F, VAN BENEDEN R et al.: Signaling molecules in overcirculation-induced pulmonary hypertension in piglets: effects of sildenafil therapy. Circulation (2004) 110:2220-2225.
108. GIAID A, SALEH D: Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary 0 hypertension. N. Engl. J. Med. (1995) 333:214-221.
109. WHARTON J, STRANGE JW, MOLLER GMO et al.: Anti-proliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am. J. Respir. Crit. Care Med. (2005) 172:105-113.
110. CARSON CC III: Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients. Curr. Urol. Rep. (1996) 4:488.
111. GHOFRANI HA, REICHENBERGER F, KOHSTALL MG et al.: Sildenafil increased: exercise capacity during hypoxia at low altitudes and at Mount Everest Base Camp. Ann. Intern. Med. (2004) 141:169-177.
112. ALDASHEV AA, KOJONAZAROV BK, AMATOV TA et al.: Phosphodiesterase type 5 and high altitude pulmonary hypertension. Thorax (2005) 60:683-687.
113. GHOFRANI HA, WIEDEMANN R, ROSE F et al.: Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet (2002) 360:895-900.
114. GUAZZI M, TUMMINELLO G, DI MARCO F, FIORENTINI C, GUAZZI MD: The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J. Am. Coll. Cardiol. (2004) 44:2339-2348.
115. ANTONIU SA: Sildenafil for pulmonary arterial hypertension: when blue turns into white. Expert Opin. Pharmacother. (2006) 7:1801-1810.
116. PAUL GA, GIBBS JS, BOOBIS AR, ABBAS A, WILKINS MR: Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension. Br. J. Clin. Pharmacol. (2005) 60:107-112.
117. SASTRY BK, NARASIMHAN C, REDDY NK, RAJU BS: Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J. Am. Coll. Cardiol. (2004) 43:1149-1153.
118. GALIE N, GHOFRANI HA, TORBICKI A et al.: Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med. (2005) 353:2148-2157.
119. WILKINS MR, PAUL GA, STRANGE JW et al.: Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH) study. Am. J. Respir. Crit. Care Med. (2005) 171:1292-1297.
120. REICHENBERGER F, VOSWINCKEL R, STEVELING E et al.: Sildenafil treatment for portopulmonary hypertension. Eur. Respir. J. (2006) 28:563-567.
121. GOMBERG-MAITLAND M, MCLAUGHLIN V, GULATI M, RICH S: Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am. J. Cardiol. (2005) 96:1334-1336.
122. HOEPER MM, FAULENBACH C, COLPON H, WINKLER J, WEITE T, NIEDERMEYER J: Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur. Respir. J. (2004) 24:1007-1010.
123. LACASSIE HJ, GERMAIN AM, VALDES G, FERNANDEZ MS, ALLAMAND F, LOPEZ H: Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet. Gynecol. (2004) 103:1118-1120.
124. HUMPL T, REYES JT, HOLTBY H, STEPHENS D, ADATHIA I: Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve month clinical trial of single-drug, open-label, pilot study. Circulation (2005) 111:3274-3280.
125. GHOFRANI HA, VOSWINCKEL R, REICHENBERGER F et al.: Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J. Am. Coll. Cardiol. (2004) 44:1488-1496.
126. ITOH T, NAGAYA N, FUJII T et al.: A combination of oral sildenafil and beraprost ameliorates pulmonary hypertension in rats. Am. J. Respir. Crit. Care Med. (2004) 169:34-38.
127. CLOZEL M, HESS P, REY M, IGLARZ M, BINKERT C, QIU C: Bosentan, sildenafil and their combination in the monocrotaline model of pulmonary hypertension in rats. Exp. Biol. Med. (2006) 231:967-973.
128. SCHERMULY RT, KREISSELMEIER KP, GHOFRANI HA et al.: Antiremodelling effects of iloprost and the dual selective phosphodiesterase III/IV inhibitor tolafentrine in chronic experimental pulmonary hypertension. Circ. Res. (2004) 94:1101-1108.
129. HUMBERT M, SIMONNEAU G: Sildenafil for pulmonary arterial hypertension: still awaiting the evidence. Am. J. Respir. Crit. Care Med. (2004) 169:6-7.
130. MCLAUGHLIN VV, OUDIZ RJ, FROST A et al.: Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. (2006) 174:1257-1263.
131. HOEPER MM, LEUCHTE H, HALANK M et al.: Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur. Resp. J. (2006) 28:691-694.
132. SIMONNEAU G, BURGESS G, COLLINGS L et al.: Safety and efficacy of combination therapy with sildenafil and epoprostenol in patients with pulmonary arterial hypertension (PAH). Proc. Am. Thorac Soc. (2006) 3:A58.
133. TANTINI B, MANES A, FIUMANA E et al.: Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res. Cardiol. (2005) 100:131-138.
134. ALI O, WHARTON J, GIBBS JS, HOWARD L, WILKINS MR: Emerging therapies for pulmonary arterial hypertension. Expert Opin. Investig. Drugs (2007) 16:803-818.
135. SCHERMULY RT, DONY E, GHOFRANI HA et al.: Reversal of experimental pulmonary hypertension by PDGF inhibition. J. Clin. Invest. (2005) 115:2811-2821.
136. GHOFRANI HA, SEEGER W, GRIMMINGER F: Imatinib for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. (2005) 353:1412-1413.
137. PETKOV V, MOSGOELLER W, ZIESCHE R et al.: Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J. Clin. Invest. (2003) 111:1339-1346.
138. ZHAO YD, COURTMAN DW, DENG Y, KUGATHASAN L, ZHANG O, STEWART DJ: Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ. Res. (2005) 96:442-450.
139. DOGGRELL SA: Rho-kinase inhibitors show promise in pulmonary hypertension. Expert Opin. Investig. Drugs (2005) 14:1157-1159.
140. HERVIÉ P, LAUNAY JM, SCROBOHACI ML et al.: Increased plasma serotonin in primary pulmonary hypertension. Am. J. Med. (1995) 99:249-254.
141. ABENHAIM L, MORIDE Y, BRENOT F et al.: Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N. Engl. J. Med. (1996) 335:609-616.
142. MARCOS E, ADNOT S, PHAM MH et al.: Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am. J. Respir. Crit. Care Med. (2003) 168:487-493.
143. KAO PN: Simvastatin treatment of pulmonary hypertension. An observational case series. Chest (2005) 127:1446-1452.
144. SANDOVAL J, ROTHMAN A, PULIDO T: Atrial septostomy for pulmonary hypertension. Clin. Chest Med. (2001) 22:547-560.
145. RASHKIND WJ: Atrial septostomy in congenital heart disease. Adv. Pediatr. (1969) 16:211-232.
146. RICH S, DODIN E, MCLAUGHLIN VV: Usefulness of atrial septostomy as a treatment for primary pulmonary hypertension and guidelines for its application. Am. J. Cardiol. (1997) 80:369-371.
147. CORRIS PA: Lung transplantation. In: Pulmonary Circulation. Diseases and their Treatment. 2nd Edition. Peacock AJ, Rubin LJ (Eds), Arnold, London (2004):309-318.
148. GALIE N, SEEGER W, NAEIJE R, SIMONNEAU G, RUBIN LJ: Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2004) 43(12 Suppl. S):S81-S88.
149. BADESCH DB, ABMAN SH, SIMONNEAU G, RUBIN LJ, MCLAUGHLIN V: Medical therapy for pulmonary arterial hypertension. Updated ACCP evidence-based clinical practice guidelines. Chest (2007) 131:1917-1928.