Treatment of Pulmonary Arterial Hypertension With Sildenafil: From Pathophysiology to Clinical Evidence

Journal of Cardiothoracic and Vascular Anesthesia

Volumn 20, Issue 5, 2006, Pages 722-735

  Raja, Shahzad G ^a   Danton, Mark D ^a   MacArthur, Kenneth J ^a   Pollock, James C ^a  

^a ROYAL HOSPITAL FOR SICK CHILDREN   (United Kingdom)

Author keywords

clinical evidence; pathophysiology; phosphodiesterase inhibitors; pulmonary hypertension; sildenafil

Indexed keywords

1 (3 CHLOROANILINO) 4 PHENYLPHTHALAZINE; 4 [2 [3 (CYCLOPENTYLOXY) 4 METHOXYPHENYL] 2 PHENYLETHYL]PYRIDINE; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; CILOMILAST; CILOSTAMIDE; DIPYRIDAMOLE; ENOXIMONE; ILOPROST; KS 505A; MILRINONE; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITOR; PROSTACYCLIN; ROLIPRAM; SIGUAZODAN; SILDENAFIL; TADALAFIL; TIBENELAST; UNCLASSIFIED DRUG; VARDENAFIL; VINPOCETINE; ZAPRINAST;

ABDOMINAL DISCOMFORT; BACKACHE; BLURRED VISION; CHILL; CLINICAL TRIAL; DATA EXTRACTION; DIZZINESS; DRUG EFFICACY; DRUG INDICATION; DRUG INDUCED HEADACHE; DRUG INHIBITION; DRUG MECHANISM; DRUG SAFETY; DYSPEPSIA; DYSPNEA; ERECTILE DYSFUNCTION; EXPERIMENTAL ANIMAL; FACE EDEMA; FLUSHING; HAND PARESTHESIA; HEART SURGERY; HEMODYNAMICS; HUMAN; HYPOTENSION; INCIDENTAL FINDING; ISCHEMIC OPTIC NEUROPATHY; MALAISE; METHODOLOGY; MONOTHERAPY; NAUSEA; NONHUMAN; NOSE CONGESTION; PATHOPHYSIOLOGY; PERIPHERAL EDEMA; PHOTOSENSITIVITY; POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RETINOPATHY; REVIEW; RHINITIS; SIDE EFFECT; VALIDITY; VISUAL DISORDER;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; 3',5'-CYCLIC-GMP PHOSPHODIESTERASES; ANIMALS; HUMANS; HYPERTENSION, PULMONARY; PIPERAZINES; PULMONARY WEDGE PRESSURE; PURINES; SULFONES; TREATMENT OUTCOME; VASODILATOR AGENTS;

EID: 33749133801     PISSN: 10530770     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.jvca.2005.12.011     Document Type: Review

References (73)

1. Gaine S.P., and Rubin L.J. Primary pulmonary hypertension. Lancet 352 (1998) 719-725
2. Farber H.W., and Loscalzo J. Pulmonary arterial hypertension. N Engl J Med 351 (2004) 1655-1665
3. Rubin L.J. Primary pulmonary hypertension. N Engl J Med 336 (1997) 111-117
4. Wanstall J.C., and Jeffery T.K. Recognition and management of pulmonary hypertension. Drugs 56 (1998) 989-1007
5. Hoeper M.M. Drug treatment of pulmonary arterial hypertension: Current and future agents. Drugs 65 (2005) 1337-1354
6. Michelakis E.D., Tymchak W., Noga M., et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 108 (2003) 2066-2099
7. Bhatia S., Frantz R.P., Severson C.J., et al. Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy. Mayo Clin Proc 78 (2003) 1207-1213
8. Bharani A., Mathew V., Sahu A., et al. The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. Indian Heart J 55 (2003) 55-59
9. Kothari S.S., and Duggal B. Chronic oral sildenafil therapy in severe pulmonary artery hypertension. Indian Heart J 54 (2002) 404-409
10. Humpl T., Reyes J.T., Holtby H., et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: Twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 111 (2005) 3274-3280
11. Raja S.G., and Nayak S.H. Sildenafil: Emerging cardiovascular indications. Ann Thorac Surg 78 (2004) 1496-1506
12. Kulkarni S.K., and Patil C.S. Phosphodiesterase 5 enzyme and its inhibitors: Update on pharmacological and therapeutical aspects. Methods Find Exp Clin Pharmacol 26 (2004) 789-799
13. Reffelmann T., and Kloner R.A. Therapeutic potential of phosphodiesterase 5 inhibition for cardiovascular disease. Circulation 108 (2003) 239-244
14. Krenzelok E.P. Sildenafil: Clinical toxicology profile. J Toxicol Clin Toxicol 38 (2000) 645-651
15. Ballard S.A., Gingell C.J., Tang K., et al. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159 (1998) 2164-2171
16. Cheitlin M.D., Hutter Jr. A.M., Brindis R.G., et al., American College of Cardiology/American Heart Association. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol 33 (1999) 273-282
17. Jackson G., Benjamin N., Jackson N., et al. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol 83 (1999) 13C-20C
18. Gillies H.C., Roblin D., and Jackson G. Coronary and systemic hemodynamic effects of sildenafil citrate: From basic science to clinical studies in patients with cardiovascular disease. Int J Cardiol 86 (2002) 131-141
19. Zusman R.M., Morales A., Glasser D.B., et al. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 83 suppl (1999) 35C-44C
20. Phillips B.G., Kato M., Pesek C.A., et al. Sympathetic activation by sildenafil. Circulation 102 (2000) 3068-3073
21. Kloner R.A., Brown M., Prisant L.M., et al. Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Am J Hypertens 14 (2001) 70-73
22. Wallis R.M. The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. Nippon Yakurigaku Zasshi 114 suppl 1 (1999) 22P-26P
23. Corbin J., Rannels S., Doss N., et al. Sildenafil citrate does not affect cardiac contractility in human or dog heart. Curr Med Res Opin 19 (2003) 747-752
24. Rabe K.F., Tenor H., Dent G., et al. Identification of PDE isozymes in human pulmonary artery and effect of selective PDE inhibitors. Am J Physiol 266 (1994) L536-L543
25. Jeffery T.K., and Wanstall J.C. Phosphodiesterase III and V inhibitors on pulmonary artery from pulmonary hypertensive rats: Differences between early and established pulmonary hypertension. J Cardiovasc Pharmacol 32 (1998) 213-219
26. Zhao L., Mason N.A., Morrell N.W., et al. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 104 (2001) 424-428
27. Ichinose F., Erana-Garcia J., Hromi J., et al. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med 29 (2001) 1000-1005
28. Traverse J.H., Chen Y.J., Du R., et al. Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exercise. Circulation 102 (2000) 2997-3002
29. Chen Y., Du R., Traverse J.H., et al. Effect of sildenafil on coronary active and reactive hyperemia. Am J Physiol Heart Circ Physiol 279 (2000) H2319-H2325
30. Ishikura F., Beppu S., Hamada T., et al. Effects of sildenafil citrate (Viagra) combined with nitrate on the heart. Circulation 102 (2000) 2516-2521
31. Dietz U., Tries H.P., Merkle W., et al. Sildenafil does not change coronary flow reserve in diabetics with erectile dysfunction. Dtsch Med Wochenschr 128 (2003) 190-195
32. Herrmann H.C., Chang G., Klugherz B.D., et al. Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 342 (2000) 1622-1626
33. Schoeffter P., Lugnier C., Demesy-Waeldele F., et al. Role of cyclic AMP- and cyclic GMP-phosphodiesterases in the control of cyclic nucleotide levels and smooth muscle tone in rat isolated aorta. A study with selective inhibitors. Biochem Pharmacol 36 (1987) 3965-3972
34. Maclean M.R., Johnston E.D., Mcculloch K.M., et al. Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: Changes in pulmonary hypertension. J Pharmacol Exp Ther 283 (1997) 619-624
35. Steiner M.K., Preston I.R., Klinger J.R., et al. Pulmonary hypertension: Inhaled nitric oxide, sildenafil and natriuretic peptides. Curr Opin Pharmacol 5 (2005) 245-250
36. Sebkhi A., Strange J.W., Phillips S.C., et al. Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 107 (2003) 3230-3235
37. Matot I., and Gozal Y. Pulmonary responses to selective phosphodiesterase-5 and phosphodiesterase-3 inhibitors. Chest 125 (2004) 644-651
38. Schermuly R.T., Kreisselmeier K.P., Ghofrani H.A., et al. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am J Respir Crit Care Med 169 (2004) 39-45
39. Jacobs W.C. Methodology and reporting of randomised controlled trials. Knee 11 (2004) 423-425
40. Raja S.G., and Dreyfus G.D. Off-pump coronary artery bypass surgery: To do or not to do? Current best available evidence. J Cardiothorac Vasc Anesth 18 (2004) 486-505
41. Tomasulo P. The NLM Gateway: Something old, something new. Med Ref Serv Q 23 (2004) 41-49
42. Greenhalgh T. How to read a paper: The Medline database. BMJ 315 (1997) 180-183
43. Sulica R., and Poon M. Medical therapeutics for pulmonary arterial hypertension: From basic science and clinical trial design to evidence-based medicine. Expert Rev Cardiovasc Ther 3 (2005) 347-360
44. Stocker C., Penny D.J., Brizard C.P., et al. Intravenous sildenafil and inhaled nitric oxide: A randomised trial in infants after cardiac surgery. Intensive Care Med 29 (2003) 1996-2003
45. Lepore J.J., Maroo A., Pereira N.L., et al. Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol 90 (2002) 677-680
46. Michelakis E., Tymchak W., Lien D., et al. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with nitric oxide. Circulation 105 (2002) 2398-2403
47. Schulze-Neick I., Hartenstein P., Li J., et al. Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease. Circulation 108 suppl 1 (2003) II167-II173
48. Ghofrani H.A., Wiedemann R., Rose F., et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomized controlled trial. Lancet 360 (2002) 895-900
49. Leuchte H.H., Schwaiblmair M., Baumgartner R.A., et al. Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Chest 125 (2004) 580-586
50. Kuhn K.P., Wickersham N.E., and Robbins I.M. Acute effects of sildenafil in patients with primary pulmonary hypertension receiving epoprostenol. Exp Lung Res 30 (2004) 135-145
51. Wilkens H., Guth A., Konig J., et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 104 (2001) 1218-1222
52. Ghofrani H.A., Wiedemann R., Rose F., et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 136 (2002) 515-522
53. Ghofrani H.A., Voswinckel R., Reighenberger F., et al. Differences in hemodynamic and oxygenation response to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension-randomized prospective study. J Am Coll Cardiol 44 (2004) 1488-1496
54. Sastry B.K., Narasimhan C., Reddy N.K., et al. Clinical efficacy of sildenafil in primary pulmonary hypertension: A randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 43 (2004) 1149-1153
55. Sheth A., Park J.E., Ong Y.E., et al. Early haemodynamic benefit of sildenafil in patients with coexisting chronic thromboembolic pulmonary hypertension and left ventricular dysfunction. Vascul Pharmacol 42 (2005) 41-45
56. Chockalingam A., Gnanavelu G., Venkatesan S., et al. Efficacy and optimal dose of sildenafil in primary pulmonary hypertension. Int J Cardiol 99 (2005) 91-95
57. Mikhail G.W., Prasad S.K., Li W., et al. Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: Acute and mid-term effects. Eur Heart J 25 (2004) 431-436
58. Ghofrani H.A., Schermuly R.T., Rose F., et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 1667 (2003) 1139-1141
59. Sastry B.K., Narasimhan C., Reddy N.K., et al. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Indian Heart J 54 (2002) 410-414
60. Ghofrani H.A., Rose F., Schermuly R.T., et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 42 (2003) 158-164
61. Wilkins M.R., Paul G.A., Strange J.W., et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med 171 (2005) 1292-1297
62. Mackway-Jones K, Carley CD, Morton RJ: Best BETs critical appraisal worksheets. Available at: http://www.bestbets.org/cgi-bin/public_pdf.pl. Accessed July 15, 2005
63. CEBM. Oxford Centre for Evidence-Based Medicine. Available at: http://www.cebm.net. Accessed July 15, 2005
64. Trachte A.L., Lobato E.B., Urdaneta F., et al. Oral sildenafil reduces pulmonary hypertension after cardiac surgery. Ann Thorac Surg 79 (2005) 194-197
65. Bentlin M.R., Saito A., De Luca A.K., et al. Sildenafil for pulmonary hypertension treatment after cardiac surgery. J Pediatr (Rio J) 81 (2005) 175-178
66. Saygili A., Canter B., Iriz E., et al. Use of sildenafil with inhaled nitric oxide in the management of severe pulmonary hypertension. J Cardiothorac Vasc Anesth 18 (2004) 775-776
67. Nemoto S., Umehara E., Ikeda T., et al. Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery. Kyobu Geka 57 (2004) 842-845
68. Lee A.J., Chiao T.B., and Tsang M.P. Sildenafil for pulmonary hypertension. Ann Pharmacother 39 (2005) 869-884
69. Marsh C.S., Marden B., and Newsom R. Severe retinopathy of prematurity (ROP) in a premature baby treated with sildenafil acetate (Viagra) for pulmonary hypertension. Br J Ophthalmol 88 (2004) 306-307
70. Pomeranz H.D., and Bhavsar A.R. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): A report of seven new cases. J Neuroophthalmol 25 (2005) 9-13
71. Kleinsasser A., Loeckinger A., Hoermann C., et al. Sildenafil modulates hemodynamics and pulmonary gas exchange. Am J Respir Crit Care Med 163 (2001) 339-343
72. Badesch D.B., Abman S.H., Ahearn G.S., et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126 suppl (2004) 35S-65S
73. News from Pfizer: FDA approves Pfizer's Revatio as treatment for pulmonary arterial hypertension. Available at: www.pfizer.com/pfizer/are/news_releases/2005pr/ mn_2005_0606.jsp. Accessed July 8, 2005