Rationale: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by in situ thrombosis and increased thromboxane A2 (Tx-M) synthesis. While both may be attributable to abnormal platelet function, there are no studies of anti-platelet therapy in IPAH.

Objectives: The purpose of this study is to assess the effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH.

This is a randomized, double-blind, placebo-controlled crossover study of aspirin 81 mg once daily and clopidogrel 75 mg once daily. Platelet function is assessed with plasma P-selectin levels and aggregometry after exposure to adenosine diphosphate, arachidonic acid, and collagen. We will assess serum levels of thromboxane B2 and urinary metabolites of thromboxane A2 and prostaglandin I2 (Tx-M and PGI-M, respectively).

Inclusion Criteria:

• Diagnosis of IPAH
• ≥ 18 years of age
• NYHA functional class I, II, or III
• Clinical stability (i.e., without change in pulmonary arterial hypertension medical regimen within one month prior to enrollment).

Exclusion Criteria:

• Other forms of PAH
• A contraindication to ASA or clopidogrel
• Thrombocytopenia (defined as platelet count ≤ 75,000)
• History of intracranial hemorrhage or chronic thromboembolic disease
• Renal failure
• Inability or unwillingness to avoid non-steroidal anti-inflammatory agents, ASA, or warfarin use for the duration of the trial