Emerging medical therapies for pulmonary arterial hypertension

Prog Cardiovasc Dis. Nov-Dec 2002;45(3):213-24. doi: 10.1053/pcad.2002.130160.


Until a few years ago, "conventional" treatment for pulmonary arterial hypertension (PAH) included oral anticoagulants, calcium channel blockers, diuretics, digoxin, and oxygen. In the 1990s, 3 randomized studies demonstrated that the continuous intravenous infusion of epoprostenol improved functional capacity, cardiopulmonary hemodynamics, and survival in patients with severe PAH. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost, and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in more than 1,100 patients. Except for terbogrel, all compounds have improved by different degrees the mean exercise capacity as assessed by 6 minutes walking distance. Conversely, these trials differ for the severity and etiology of included PAH patients as well as for the effects on combined clinical events, on quality of life, and on hemodynamics. No trials have shown effects on mortality, and each new compound presents different side effects that seem unpredictable in the individual patient. At present, additional new compounds such as sitaxentan, ambisentan, L-arginine, and sildenafil are studied in clinical trials. The new therapeutic options are currently in different phases of approval by regulatory agencies, and when they will become available we will have the opportunity to select the most appropriate treatment for the single patient, according to an individualized benefit-to-risk ratio.

Publication types

  • Review

MeSH terms

  • Arginine / therapeutic use
  • Bosentan
  • Controlled Clinical Trials as Topic
  • Drug Therapy, Combination
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / metabolism
  • Epoprostenol / therapeutic use
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology
  • Iloprost / therapeutic use
  • Nitric Oxide / metabolism
  • Piperazines / therapeutic use
  • Platelet Aggregation Inhibitors / therapeutic use
  • Purines
  • Pyridines / therapeutic use
  • Signal Transduction / drug effects
  • Sildenafil Citrate
  • Sulfonamides / therapeutic use
  • Sulfones
  • Thromboxane A2 / metabolism
  • Vasodilator Agents / therapeutic use


  • Endothelin-1
  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purines
  • Pyridines
  • Sulfonamides
  • Sulfones
  • Vasodilator Agents
  • Nitric Oxide
  • beraprost
  • Thromboxane A2
  • terbogrel
  • Arginine
  • Sildenafil Citrate
  • Epoprostenol
  • Iloprost
  • Bosentan
  • treprostinil