Current and emerging therapy for primary pulmonary hypertension.
OBJECTIVE
To review the epidemiology, pathophysiology, clinical symptoms, and diagnostic workup of primary pulmonary hypertension (PPH) and to discuss the available data on the current and emerging therapies being used to treat this disorder.


METHODS
Primary and review articles were identified with a MEDLINE search (1966-December 2001) and through secondary sources.


METHODS
All articles identified from the data sources were evaluated and all information deemed relevant was included in this review.


RESULTS
In the absence of a definable cause, PPH is a disorder classified by a progressive increase in pulmonary vascular resistance and mean pulmonary artery pressure. A relatively rare condition, PPH has an annual incidence of 1-2 cases per million people, slightly higher in women than men. The prognosis is poor, with a mean survival time of 2.8 years after diagnosis if untreated. Vasoconstriction, vascular remodeling, and thrombosis are hallmarks of the disease process. Anticoagulation and vasodilators are the most commonly employed treatment options, showing benefits in clinical outcomes, hemodynamic parameters, and mortality. Several new vasodilators are being evaluated for the treatment of PPH. Bosentan was recently approved as the first oral agent for the treatment of PPH. Iloprost, treprostinil, and beraprost are investigational agents in Phase III studies.


CONCLUSIONS
Until additional studies and experience with these agents become available, calcium-channel blockers (CCBs) remain the first option for therapy. For patients not responding to CCBs, therapeutic options will now include epoprostenol and bosentan. Since there are no comparison trials between these 2 agents, therapeutic decisions should be based on patient-specific concerns. Clinical data and experience support the use of epoprostenol; however, in patients at risk or considered unsuitable candidates, bosentan may become a preferred option. Additional studies are warranted to address the potential therapeutic benefits of combination therapy and long-term benefits of agents to treat PPH.
College of Pharmacy, University of Cincinnati, OH, USA. passse@healthall.com
Steven E
SE
Pass
Michelle L
ML
Dusing
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000627:therapeutic use; D008297:Male; D014665:Vasodilator Agents / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol; D016285:Iloprost