Skip to main content

Prostacyclin Therapy for Pulmonary Arterial Hypertension

  • Chapter
Pulmonary Hypertension

Part of the book series: Contemporary Cardiology™ ((CONCARD))

Abstract

The first class of agents approved specifically for the therapy of pulmonary hypertension in the United States, the prostacyclins have assumed a key treatment role, especially via the intravenous route for class IV patients. The best established agent for efficacy and the only one shown to significantly improve survival is epoprostenol via continuous intravenous infusion. Epoprostenol also improves symptoms, exercise capacity, and pulmonary hemodynamics in IPAH patients. While the literature is not as voluminous in patients with PAH associated with other disorders, epoprostenol therapy improves the symptoms of PAH in many of these patients. Enthusiasm for epoprostenol must be tempered by its cumbersome intravenous delivery system and inherent risks. Newer prostacyclins include treprostinil, available in subcutaneous and intravenous forms, and inhaled iloprost. Each has established efficacy in randomized trials. Subcutaneous treprostinil has been plagued by infusion site pain but is a good alternative for those who can tolerate it. Inhaled iloprost is being used increasingly because the inhaled route has fewer systemic side effects and improves oxygenation compared to the intravenous route, and an improved administration system makes it more tolerable for patients. Whichever of the prostacyclins is chosen, patients are monitored closely thereafter because of the many potential complications and since most forms require timely dose increases because of tolerance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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; 327:70–7.

    PubMed  CAS  Google Scholar 

  2. 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(7):485–91.

    PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease: A randomized, controlled trial. Ann Intern Med 2000; 132:425–34.

    PubMed  CAS  Google Scholar 

  5. Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999; 99:1858–65.

    PubMed  CAS  Google Scholar 

  6. Aguilar RV, Farber HW. Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med 2000; 162(5):1846–50.

    PubMed  CAS  Google Scholar 

  7. McLaughlin VV, Genthner DE, Panella MM, Hess DM, Rich S. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: A case series. Ann Intern Med 1999; 130:740–3.

    PubMed  CAS  Google Scholar 

  8. Bresser P, Fedullo PF, Auger WR, et al. Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension. Eur Respir J 2004 Apr; 23(4):595–600.

    Google Scholar 

  9. Barst RJ, McGoon M, McLaughlin V, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003; 41:2119–25.

    Article  PubMed  CAS  Google Scholar 

  10. Moncada S, Gryglewski R, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976; 263:663–5.

    Article  PubMed  CAS  Google Scholar 

  11. Moncada S. Prostacyclin, EDRF and atherosclerosis. Adv Exp Med Biol 1988; 243:1–11.

    PubMed  CAS  Google Scholar 

  12. Dinh-Xuan AT. Endothelial modulation of pulmonary vascular tone. Eur Respir J 1992 Jun; 5(6):757–62.

    Google Scholar 

  13. Chen YF, Oparil S. Endothelial dysfunction in the pulmonary vascular bed. Am J Med Sci 2000; 320:223–32.

    Article  PubMed  CAS  Google Scholar 

  14. Skoglund ML, Nies AS, Gerber JG. Inhibition of acid secretion in isolated canine parietal cells by prostaglandins. J Pharmacol Exp Ther 1982; 220:371–4.

    PubMed  CAS  Google Scholar 

  15. 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; 159:1925–32.

    PubMed  CAS  Google Scholar 

  16. Friedman R, Mears G, Barst RJ. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation 1997; 96:2782–4.

    PubMed  CAS  Google Scholar 

  17. Sakamaki F, Kyotani S, Nagaya N, et al. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation 2000; 102:2720–5.

    PubMed  CAS  Google Scholar 

  18. Jones DK, Higenbottam TW, Wallwork J. Treatment of primary pulmonary hypertension intravenous epoprostenol (prostacyclin). Br Heart J 1987; 57:270–8.

    Article  PubMed  CAS  Google Scholar 

  19. 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; 121:409–15.

    PubMed  CAS  Google Scholar 

  20. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: A national prospective study. Ann Intern Med 1987; 107:216–23.

    PubMed  CAS  Google Scholar 

  21. 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; 30:343–9.

    Article  PubMed  CAS  Google Scholar 

  22. McLaughlin VV, Genthner DE, Panella MM, Rich S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998; 338: 273–7.

    Article  PubMed  CAS  Google Scholar 

  23. Wax D, Garofano R, Barst RJ. Effects of long-term infusion of prostacyclin on exercise performance in patients with primary pulmonary hypertension. Chest 1999; 116:914–20.

    Article  PubMed  CAS  Google Scholar 

  24. Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997 Feb 27; 63(4):604–6.

    Article  PubMed  CAS  Google Scholar 

  25. McLaughlin V, Shillington A, Rich S. Survival in primary pulmonary hypertension: The impact of epoprostenol therapy. Circulation 2002; 106:1477–82.

    Article  PubMed  CAS  Google Scholar 

  26. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: Prognostic factors and survival. J Am Coll Cardiol 2002; 40(4):780–8.

    Article  PubMed  CAS  Google Scholar 

  27. Kuhn KP, Byrne DW, Arbogast PG, Doyle TP, Loyd JE, Robbins IM. Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. Am J Respir Crit Care Med 2003; 167: 580–6.

    Article  PubMed  Google Scholar 

  28. Conte JV, Gaine SP, Orens JB, Harris T, Rubin LJ. The influence of continuous intravenous prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation. J Heart Lung Transplant 1998; 17(7):679–85.

    PubMed  CAS  Google Scholar 

  29. Sueta CA, Gheorghiade M, Adams KF Jr., et al. Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group. Am J Cardiol 1995 Jan 19; 75(3):34A–43A.

    Google Scholar 

  30. Oates, JA, Fitzgerald GA, Branch RA, Jackson EK, Knapp HR, Roberts LJ. Clinical implications of prostaglandin and thromboxane A2 formation. N Engl J Med 1998; 319: 761–7.

    Google Scholar 

  31. Rich S, McLaughlin VV. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999; 34:1184–7.

    Article  PubMed  CAS  Google Scholar 

  32. McLaughlin VV, Gaine SP, Barst RJ, et al. Efficacy and safety of treprostinil: An epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol 2003; 41:293–9.

    Article  PubMed  CAS  Google Scholar 

  33. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: A double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002; 165:800–4.

    PubMed  Google Scholar 

  34. Oudiz RJ, Schilz RJ, Barst RJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest 2004; 126:420–7.

    Article  PubMed  CAS  Google Scholar 

  35. Laliberte K, Arneson C, Jeffs R, et al. Pharmacokinetics and steady state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous routes to normal volunteers. J Cardiovasc Pharmacol 2004; 44:209–14.

    Article  PubMed  CAS  Google Scholar 

  36. 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; 172:1586–9.

    Article  PubMed  Google Scholar 

  37. Bloodstream infections among patients treated with intravenous epoprostenol or intravenous treprostinil for pulmonary arterial hypertension —Seven sites 2003–2006. Morb Mort Wkly Rep 2007; 56:170–2.

    Google Scholar 

  38. Sandifer BL, Brigham KL, Lawrence EC, Mottola D, Cuppels C, Parker RE. Potent effects of aerosol compared to intravenous treprostinil on the pulmonary circulation. J Appl Physiol 2005; 99:2363–8.

    Article  PubMed  Google Scholar 

  39. Voswinckel R, Enke B, Reichenberger F, et al. Favorable effects of inhaled treprostinil in severe pulmonary hypertension: Results from randomized controlled pilot studies. J Am Coll Cardiol 2006 Oct 17; 48(8):1672–81.

    Article  PubMed  Google Scholar 

  40. Krause W, Krais T. Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man. Eur J Clin Pharmacol 1986; 30: 61–8.

    Article  PubMed  CAS  Google Scholar 

  41. Olschewski H, Walmrath D, Schermuly R, Ghofrani A, Grimminger F, Seeger W. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996; 124:820–4.

    PubMed  CAS  Google Scholar 

  42. Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002; 347:322–9.

    Article  PubMed  CAS  Google Scholar 

  43. 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 Jun 22; 342(25):1866–70.

    Google Scholar 

  44. Wonisch M, Fruhwald FM, Maier R, et al. Continuous haemodynamic monitoring during exercise in patients with pulmonary hypertension. Int J Cardiol 2005; 101:415–20.

    Article  PubMed  Google Scholar 

  45. 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; 26:1895–902.

    Google Scholar 

  46. Schenk P, Petkov V, Madl C, et al. Aerosolized iloprost therapy could not replace long-term IV epoprostenol (prostacyclin) administration in severe pulmonary hypertension. Chest 2001; 119:296–300.

    Article  PubMed  CAS  Google Scholar 

  47. Olschewski H, Ghofrani HA, Walmrath D, et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med 1999; 160:600–7.

    PubMed  CAS  Google Scholar 

  48. 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; 174:1257–63.

    Article  PubMed  Google Scholar 

  49. Suzuki H, Sato S, Tanabe S, Hayasaka K. Beraprost sodium for pulmonary hypertension with congenital heart disease. Pediatr Int 2002; 44:528–9.

    Article  PubMed  Google Scholar 

  50. Nagaya N, Uematsu M, Okano Y, et al. Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. J Am Coll Cardiol 1999; 34:1188–92.

    Article  PubMed  CAS  Google Scholar 

  51. Galie N, Humbert M, Vachiery JL, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: A randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2002; 39:1496–502.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, Totowa, NJ

About this chapter

Cite this chapter

Hill, N.S., Vardas, T.F., McLaughlin, V. (2008). Prostacyclin Therapy for Pulmonary Arterial Hypertension. In: Hill, N.S., Farber, H.W. (eds) Pulmonary Hypertension. Contemporary Cardiology™. Humana Press. https://doi.org/10.1007/978-1-60327-075-5_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-075-5_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-661-0

  • Online ISBN: 978-1-60327-075-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics