Official journal of the Slovak Society of Cardiology,
Slovak Society of Hypertension and Slovak Association for Cardiac Arrhythmias

Cardiology Letters 2012, 21(3):192-200

Contemporary treatment of pulmonary arterial hypertension.

Luknár M, Lesný P, Varga I, Solík P, Kučerová D, Gonçalvesová E
Centrum pre pľúcnu artériovú hypertenziu Národný ústav srdcových a cievnych chorôb a.s., v Bratislave, Slovenská republika

Pulmonary arterial hypertension (PAH) is a rare, devastating, and incurable disease. Pathological and pathophysiological changes include vasoconstriction, remodelling, proliferation, and thrombosis. They result in pressure overload and failure of the right ventricle. Recently, treatment options have been introduced that improve quality of life and survival of PAH patients. This review summarizes contemporary treatment options and therapeutic strategy in PAH. PAH treatment is characterized by the lack of scientific evidence. Traditionally, it comprises supportive, conventional and specific treatment, and interventional/surgical approaches. Supportive and conventional treatment includes lifestyle changes, warfarin, diuretics, and other. Specific treatment is aimed directly at the basic pathogenetic mechanisms of PAH. It consists of calcium channel blockers, prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. All therapies approved for PAH have mainly accomplished the improvement of physical capacity, symptoms, and delay in the time to clinical worsening in short-term randomized studies and long-term non-randomized observations. A single randomized study and some metaanalyses and registry data indicate a positive influence on survival with modern drug treatment. Interventional and surgical options represent advanced approaches for highly selected patients. Treatment strategy is based on a consensus algorithm. A major role is played by periodic evaluation of treatment success using complex prognostic criteria. PAH requires therapeutic management in a specialized centre having sufficient experience. Tab. 2, Fig. 2, Ref. 53, Online full text (Free PDF),

Keywords: pulmonary arterial hypertension; treatment; prostanoids; endothelin antagonists; phosphodiesterase type 5 inhibitors; lung transplantation

Published: March 1, 2012  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Luknár M, Lesný P, Varga I, Solík P, Kučerová D, Gonçalvesová E. Contemporary treatment of pulmonary arterial hypertension. Cardiology Letters. 2012;21(3):192-200.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Greyson CR. The right ventricle and pulmonary circulation: basic concepts. Rev Esp Cardiol 2010;63:81-95. Go to original source...
    2. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation 2006; 114(13):1417-1431. Go to original source...
    3. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343-349. Go to original source...
    4. Galiè N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 2009;30(4):394-403. Go to original source...
    5. Galiè N, Hoeper MM, Humbert M, 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;30(20):2493-537. Go to original source...
    6. Fox BD, Kassirer M, Weiss I, et al. Ambulatory rehabilitation improves exercise capacity in patients with pulmonary hypertension. J Card Fail 2011;17(3):196-200. Go to original source...
    7. Bedard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009;30:256-265. Go to original source...
    8. Weitzenblum E, Sautegeau A, Ehrhart M, et al. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1985;131:493-498. Go to original source...
    9. Hoeper MM, Sosada M, Fabel H. Plasma coagulation profiles in patients with severe primary pulmonary hypertension. Eur Respir J 1998;12:1446-1449. Go to original source...
    10. Chaouat A, Weitzenblum E, Higenbottam T. The role of thrombosis in severe pulmonary hypertension. Eur Respir J 1996;9(2):356-363. Go to original source...
    11. Fuster V, Steele PM, Edwards WD, et al. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984;70(4):580-587. Go to original source...
    12. Provencher S, Herve P, Jais X, et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology 2006;130(1):120-126. Go to original source...
    13. McCollister DH, Beutz M, McLaughlin V, et al. Depressive symptoms in pulmonary arterial hypertension: prevalence and association with functional status. Psychosomatics. 2010;51(4):339-339e8. Go to original source...
    14. Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005;111(23):3105-3111. Go to original source...
    15. 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(9):1023-1030. Go to original source...
    16. Solík P, Lesný P, Luknár M, et al. The long-term response to treatment with calcium channel blockers in a patient with idiopathic pulmonary arterial hypertension. Bratisl Lek Listy, in press
    17. Jones DA, Benjamin CW, Linseman DA. Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol 1995;48:890-896. Go to original source...
    18. Tuder RM, Cool CD, Geraci MW, 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. Go to original source...
    19. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351(14):1425-1436. Go to original source...
    20. Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 1990;112:485-491. Go to original source...
    21. Barst, RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994;121:409-415. Go to original source...
    22. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 1996;334(5):296-302. Go to original source...
    23. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002;106:1477-1482. Go to original source...
    24. Laliberte K, Arneson C, Jeffs R, et al. Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin®) administered by the intravenous and subcutaneous route to normal volunteers. J Cardiovasc Pharmacol 2004;44(2):209-214. Go to original source...
    25. Skoro-Sajer N, Lang IM, Harja E, et al. A clinical comparison of slow- and rapid-escalation treprostinil dosing regimens in patients with pulmonary hypertension. Clin Pharmacokinet 2008;47(9):611-618. Go to original source...
    26. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analog, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165:800-804. Go to original source...
    27. Lang I, Gomez-Sanchez M, Kneussl M, et al. Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest 2006;129(6):1636-1643. Go to original source...
    28. Olschewski H, Simonneau G, Galiè N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347: 322-329. Go to original source...
    29. Giaid A, Yanagisawa 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. Go to original source...
    30. Opitz CF, Ewert R, Kirch W, et al. Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J 2008;29(16):1936-1948. Go to original source...
    31. Channick R, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001;358:1119-1123. Go to original source...
    32. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896-903. Go to original source...
    33. Galiè N, 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. Go to original source...
    34. Galiè N, Rubin LJ, Hoeper M, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 2008;371:2093-2100. Go to original source...
    35. 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. Go to original source...
    36. Humbert M, Segal ES, Kiely DG, et al. Results of European postmarketing surveillance of bosentan in pulmonary hypertension. Eur Respir J 2007;30:338-344. Go to original source...
    37. Galiè N. Badesch D, Oudiz R, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005;46:529-535. Go to original source...
    38. Galiè, N. Olschewski H, Oudiz RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 2008;117:3010-3019. Go to original source...
    39. Oudiz RJ, Galiè N, Olschewski H, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54(21):1971-1981. Go to original source...
    40. Giaid A. Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995;333,214-221. Go to original source...
    41. Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. N Engl J Med 2005;353(20):2148-2157. Go to original source...
    42. Rubin LJ, Badesch DB, Fleming TR, et al. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: SUPER-2. Chest 2011;140(5):1274-1278. Go to original source...
    43. Roberts KE, Preston IR. Safety and tolerability of bosentan in the management of pulmonary arterial hypertension Drug Des Devel Ther 2009;3:111-118. Go to original source...
    44. Venitz J, Zack J, Gillies H, et al. Clinical Pharmacokinetics and Drug-Drug Interactions of Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension. J Clin Pharmacol 2011 Dec 28. [Epub ahead of print])
    45. Hoeper MM, Markevych I, Spiekerkoetter E, et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J 2005;26:858-863. Go to original source...
    46. 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;174:12571263. Go to original source...
    47. Simonneau G, Rubin L, Galie N, et al. for the Pulmonary Arterial Hypertension combination Study of Epoprostenol and Sildenafil (PACES) Study Group. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension. Ann Intern Med 2008;149:521-530. Go to original source...
    48. McLaughlin VV, Benza RL, Rubin LJ, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 2010;55(18):1915-1922. Go to original source...
    49. Delcroix M, Spaas K, Quarck R. Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostracyclin therapy. Eur Resp Rev 2009;18:114:253-259. Go to original source...
    50. Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010;122:156-163. Go to original source...
    51. O'Callaghan DS, Savale L, Montani D, et al. Treatment of pulmonary arterial hypertension with targeted therapies. Nat Rev Cardiol 2011;8:526-538. Go to original source...
    52. Sandoval J, Gaspar J, Pulido T. Atrial septostomy for the treatment of severe pulmonary hypertension. In: Humbert M, Lynch JP III. (Eds). Pulmonary hypertension. New York: Informa Healthcare; 2009:288-400.
    53. Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report-2011. J Heart Lung Transplant 2011; 30(10):1071-1132. Go to original source...

    Return to the content