Anastrozole in Patients With Pulmonary Arterial Hypertension

Inclusion criteria

• Previous documentation of mean pulmonary artery pressure > 25 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) < 16 mm Hg and PVR > 3 WU at any time before study entry.
• Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, congenital heart disease, portal hypertension, or HIV infection.
• Most recent pulmonary function tests with FEV1/FVC >50% AND either a) total lung capacity > 70% predicted or b) total lung capacity between 60% and 70% predicted with no more than mild interstitial lung disease on computerized tomography scan of the chest
• Ability to perform six minute walk testing without limitations in musculoskeletal function or coordination.
• If female, post-menopausal state, defined as:
• > 50 years old AND
• a) have not menstruated during the preceding 12 months OR
• b) have follicle-stimulating hormone (FSH) levels (> 40 IU/L) OR
• < 50 years and FSH (> 40 IU/L) OR
• having had a bilateral oophorectomy
• Informed consent

Exclusion criteria

• Treatment with estrogen or anti-hormone therapy (tamoxifen, fulvestrant, etc.)
• WHO Class IV functional status
• History of breast cancer
• Clinically significant untreated sleep apnea
• 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 < 45% on echocardiography
• Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors) within three months of enrollment; the dose must be stable for at least 3 months prior to Baseline Visit
• Hormone therapy
• Hospitalized or acutely ill
• Renal failure (creatinine > 2.0)
• Child-Pugh Class C cirrhosis
• Current or recent (< 6 months) chronic heavy alcohol consumption
• Current use of another investigational drug (non-FDA approved) for PAH
• Enrollment in a clinical trial within one month of screening
• Age < 18