A Study of Aspirin and Simvastatin in Pulmonary Arterial Hypertension

Inclusion Criteria: * Mean pulmonary artery pressure greater than 25 mm Hg at rest with a pulmonary capillary wedge pressure less than 16 mm Hg * Diagnosis of PAH that is a) idiopathic, b) familial, or c) associated with collagen vascular disease, HIV infection, congenital systemic-to-pulmonary shunt, or former anorexigen use * Most recent pulmonary function tests showing FEV1/FVC ratio greater than 50% AND one of the following conditions: a) total lung capacity greater than 70% predicted, or b) total lung capacity between 60% and 70% of predicted value with no more than mild patchy interstitial lung disease on high resolution computerized tomography of the chest * Ability to perform six-minute walk testing without limitations in musculoskeletal function or coordination * Negative pregnancy test at screening visit for women of childbearing potential * If female, willing to use adequate form of birth control Exclusion Criteria: * PAH related to other etiologies * Diagnosis of sickle cell disease * Clinically significant untreated sleep apnea, as diagnosed by polysomnography * Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection fraction less than 45% on echocardiography * Hospitalized or acutely ill * Kidney failure * Initiation of PAH therapy (prostacyclin analogues, endothelin \[ET\]-1 receptor antagonists, phosphodiesterase \[PDE\]-5 inhibitors) within 3 months of study entry * Allergy or hypersensitivity to aspirin or simvastatin * Absolute indication for aspirin or other anti-platelet therapy * Current treatment with statin therapy * Inability or unwillingness to avoid non-steroidal, anti-inflammatory medications for 6 months following study entry * Current or recent use or planned treatment with one of the following: amiodarone, cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, cimetidine, danazol, large quantities of grapefruit juice (more than 1 quart daily), verapamil, fibrates, or niacin * Peptic or duodenal ulcer diagnosed within 1 year of study entry * Gastrointestinal bleeding within 6 months prior of study entry * Bleeding diathesis * History of intracranial bleeding * Anemia (hematocrit less than 30%) at screening * International normalized ratio (INR) greater than 3.0 at screening * Severe thrombocytopenia (less than 75,000/L) at screening * Hepatic transaminases greater than twice the upper limit of normal at screening * Chronic liver disease (e.g., cirrhosis, chronic hepatitis) with portal hypertension * Current or recent (within 6 months of study entry) chronic heavy alcohol consumption * History of myositis * Creatine phosphokinase (CPK) greater than 1.5 times the upper limit of normal at screening * Abnormalities of the arm or hand or past radical mastectomy that might prevent brachial artery ultrasound * Pregnant or breastfeeding * Current use of another investigational drug for PAH * Received a lung transplant