Atorvastatin Therapy to Improve Endothelial Function in Sickle Cell Disease

Exclusion Criteria

• •Clinically unstable sickle cell disease defined as having an acute pain crisis within the last week.
• •Current pregnancy or lactation.
• •Conditions that may independently affect endothelial function:
• •Diabetes mellitus or fasting blood sugar greater than 120 mg/dL
• •Cigarette smoking within one month
• •Hypertension (diastolic blood pressure greater than 90 mmHg)
• •Serum creatinine greater than 1.5 mg/dL
• •Hemoglobin less than or equal to 6 g/dL; however, patients may return for evaluation at a later date.
• •Recent transfusion (last 4 weeks).
• •No aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) for one week and no caffeine the day of the study. Patients on opiates or acetaminophen will not be excluded.
• •Subjects taking sildenafil, vardenafil, L-arginine, fibrates (e.g., clofibrate, gemfibrozil, or fenofribrate) or inhaled nitric oxide within the last week will be excluded from the study.
• •Subjects taking any statin drug (e.g., fluvastatin, lovastatin, pravastatin, or simvastatin) within the last four weeks will be excluded from the study.
• •Subjects taking drugs with known clinically significant metabolic interactions with statins (via metabolism through cytochrome P450 3A4):
• •Ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, azithromycin, cyclosporine, tacrolimus, fibric acid derivatives, niacin (nicotinic acid).
• •Subjects who have obstructive or vasospastic vascular disease.
• •Subjects with significant cardiac disease and/or ECG abnormalities.
• •Subjects with significant hypotension.
• •Women who do not use two forms of birth control while participating in this study.
• •Current pregnancy or lactation.
• •Conditions that may independently affect endothelial function:
• •Diabetes mellitus or fasting blood sugar greater than 120 mg/dL
• •Cigarette smoking within one month
• •Hypertension (diastolic blood pressure greater than 90 mmHg)
• •Serum creatinine greater than 1.5 mg/dL
• •Serum alanine aminotransferase (ALT) greater than 3 times the upper limit of normal.
• •Hemoglobin less than 12 g/dL; however, patients may return for evaluation at a later date.
• •No aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) for one week and no caffeine the day of the study. Patients on opiates or acetaminophen will not be excluded.
• •Subjects taking sildenafil, vardenafil, L-arginine, fibrates (e.g., clofibrate, gemfibrozil, or fenofribrate) or inhaled nitric oxide within the last week will be excluded from the study.
• •Subjects taking any statin drug (e.g., fluvastatin, lovastatin, pravastatin, or simvastatin) within the last four weeks will be excluded from the study.
• •Subjects who have obstructive or vasospastic vascular disease.
• •Subjects with significant cardiac disease and/or ECG abnormalities.
• •Subjects with significant hypotension.
• •Subjects with any known form of hemolytic anemia, including sickle cell disease (Hb SS, SC, S-beta-thalassemia, or other known sickling syndromes; sickle trait will NOT be excluded).