Simvastatin Therapy for Moderate and Severe COPD

COPD exacerbation is a common complication that significantly contributes to the high
morbidity, mortality and costs associated with COPD. COPD exacerbations are associated with
heightened lung inflammation that may have systemic implications (e.g., peripheral muscle
weakness, cognitive impairment, depression, stroke, acute coronary syndrome, and
atherosclerosis). Statins are potent agents that significantly reduce vascular events in
patients with increased risks due to prior cardiac or cerebral vascular events and elevated
lipid profiles. Statins have pleiotropic effects that extend well beyond their lipid lowering
effects and may be potent anti-inflammatory agents. Retrospective data conducted in COPD
patients indicate that statin use is associated with markedly decreased rates of COPD
hospitalization and stabilization of lung function. Decreases in mortality in COPD due to
complications of flu-like illnesses and deaths due to cardiovascular events have also been
reported. Inflammatory biomarkers (C-reactive protein and interleukin- 6) are reported to be
elevated in moderate to severe COPD patients who are prone to exacerbations. Inflammatory
biomarkers (C-reactive protein and interleukin- 6) are reported to be reduced by statin
therapy in patients with hyperlipidemia and cardiovascular diseases. Treatments that can
effectively lessen the prevalence and severity of COPD exacerbations are desperately needed

Inclusion Criteria:

1. Male and female subjects, 40-80 years of age.

2. Clinical diagnosis of at least moderate COPD as defined by the GOLD criteria:

1. Postbronchodilator FEV1(forced expiratory volume at one second)/FVC(forced vital
capacity) < 70%,

2. Postbronchodilator FEV1 (forced expiratory volume at one second) < 80% predicted,
with or without chronic symptoms (i.e., cough, sputum production).

3. Cigarette consumption of 10 pack-years or more. Patients may or may not be active
smokers.

4. Must meet one or more of the following 4 conditions

1. Be using supplemental oxygenate

2. Receiving a course of systemic corticosteroids and/or antibiotics for respiratory
problems in the past year,

3. Visiting an Emergency Department for a COPD exacerbation within the past year, or

4. Being hospitalized for a COPD (Chronic Obstructive Pulmonary Disease)
exacerbation within the past year

5. Willingness to make return visits and availability by telephone for duration of study.

6. Free of active coronary disease

7. Subject with expected life expectancy > 36 months

Exclusion Criteria:

1. Patients who:

1. are on statin drugs.

2. should be on statins based on established risk stratification using the ATP-III
(Adult Treatment Panel) to determine 10 year risk.

2. Documented history of active coronary heart disease, such as unstable angina, prior
myocardial infarction, stroke, symptomatic peripheral vascular or carotid artery
disease, or congestive heart failure within the past 3 months.

3. A diagnosis of asthma.

4. The presence of a diagnosis other than COPD that results in the patient being either
medically unstable, or having a predicted life expectancy < 3 years.

5. Special patient groups: prisoners, pregnant women, institutionalized patients

6. Women who are at risk of becoming pregnant during the study (pre-menopausal) and who
refuse to use acceptable birth control (hormone-based oral or barrier contraceptive)
for the duration of the study.

7. Woman using estradiol compounds for contraception. Postmenopausal women on estradiol
compounds for hormone replacement therapy will be allowed into the trial.

8. Participants otherwise meeting the inclusion criteria will not be enrolled until they
are a minimum of four weeks from their most recent acute exacerbation.

9. A clinical diagnosis of bronchiectasis defined as production of > one-half cup of
purulent sputum/day.

10. Participants using niacin, azole antifungals (itraconazole, ketoconazole,
posaconazole), fibric acid derivatives, erythromycin, clarithromycin, telithromycin,
diltiazem, amlodipine , ranolazine,HIV protease inhibitors (such as indinavir),
amiodarone, gemfibrozil, cyclosporine, verapamil, danazol, nefazodone, and red yeast
rice extracts are excluded

11. Active liver disease. Active liver disease is defined as ALT (alanine
aminotransferase), AST (aspartate aminotransferase) as greater than 1.5 times the
upper limit of normal.

12. Patients with renal failure defined by serum creatinine greater than 3mg/dl.

13. Alcoholism. Alcoholism is defined as > 35 drinks per week. A drink is defined as one
bottle of beer, one 8-ounce glass of wine, or one ounce of hard liquor.

14. Hypersensitivity to HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase
inhibitors. Hypersensitivity is defined as an allergic reaction to statin, prior
history of myopathy, rhabdomyolysis or previous intolerance to statin use.

15. Participants drinking greater than 4 cups (1qt) of grapefruit juice per day.

16. Participants drinking greater than 3 cups of green tea per day.

17. Diabetics will be excluded. Diabetics are defined by:

1. A CURRENT physician diagnosis of diabetes OR 2. CURRENT use of diabetic meds OR 3.
Elevated HbA1c > 6.5% 18. The discretion of the Principal Investigator that the potential
participant will not be a reliable study subject to complete the study requirements.