Stop Atherosclerosis in Native Diabetics Study
Stop Atherosclerosis in Native Diabetics Study
Compared to standard treatment goals achieving lower targets for LDL cholesterol (bad
 cholesterol) and blood pressure in people with diabetes will slow the progression of
 atherosclerosis as measured by carotid artery thickness, and reduce clinical cardiovascular
 events such as heart attacks and strokes. This study is a randomized 3-year trial. The
 primary endpoint will be a combination of various measures of the carotid artery, (which is
 an easy, non-invasive way to detect cardiovascular disease) and events such as heart attacks
 and strokes. The study will also look at secondary endpoints such as how well the heart
 pumps, fat,protein and inflammatory markers in the blood,and kidney function. The study
 enrolled 549 American Indian men and women with diabetes, > 40 years of age and is being
 conducted in four field centers involving Indian Health Service/Tribal primary care
 facilities in Phoenix/Sacaton, Arizona; Chinle, Arizona; Rapid City/Pine Ridge, South Dakota;
 and Lawton, Oklahoma, with input from American Indian physicians and community members.
Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk
 for CVD, the major cause of death in diabetic individuals. The conventional cardiovascular
 risk factors of hyperlipidemia and hypertension add to the progression of diabetic vascular
 disease. Appropriate treatment targets for LDL-C and blood pressure in diabetic individuals
 are currently being debated. The Stop Atherosclerosis in Native Diabetics Study is a
 randomized, open label, 3-year, clinical trial to examine the effects of aggressive LDL-C
 (goal < 70 mg/dL) and BP (goal < 115/75 mm Hg) reduction versus the standard goals of < 100
 mg/dL for LDL-C and < 130/85 mmHg for BP. Five hundred forty-nine American Indian men and
 women > age 40 with type 2 diabetes were randomized to one of two groups. Lipids and BP are
 managed using FDA-approved medications in an algorithmic approach. The presence and
 progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography
 assesses cardiac function. The primary endpoint is the composite outcome of change in carotid
 artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are
 combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a
 cardiovascular event. Secondary endpoints include carotid plaque score, left ventricular
 geometry and function, serum CRP, and safety measures. Unique aspects of the study design and
 analysis plan involve changes during the trial of LDL-C treatment goals for participants with
 baseline or incident CVD in the conventional group, because of changes in the standard of
 care, and the use of a composite outcome. Study results will be valuable in understanding the
 effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in
 diabetic individuals in all U.S. populations and will provide evidence for determining
 optimal LDL-C and BP treatment goals for diabetic patients.
Inclusion Criteria:

 1. American Indian men and women 40 years of age or older

 2. Type 2 DM (according to 1997 ADA criteria and/or previously diagnosed by former ADA or
 WHO criteria): fasting plasma glucose >= 7.0 mmol/L (126 mg/dL) or 2-hour glucose >=
 11.0 mmol/L (>200 mg/dL) after a 75-gram oral glucose tolerance test.

 3. LDL cholesterol >= 100 mg/dL. within the previous 12 months.

 4. Systolic BP >= 130 mm Hg. within the previous 12 months.

 Exclusion Criteria:

 1. New York Heart Association Stage III- IV congestive heart failure.

 2. SBP >180 mmHg (2% of population) or patients with known causes of hypertension.

 3. History of angioedema.

 4. Any medical condition that study physicians believe would interfere with study
 participation or evaluation of results.

 5. Mental incapacity and/or cognitive impairment on the part of the patient that would
 preclude adequate understanding of, or cooperation with, the study protocol.

 6. Serum hepatic transaminase levels  2X the upper limit of normal.

 7. Participation in any clinical trial of any investigational medication within 3 months
 prior to this trial.

 8. Renal insufficiency as indicated by serum creatinine >2.0 for women and >2.4 for men.

 9. Diagnosis of primary hyperlipidemia in medical record.

 10. Secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome. Patients
 on stable doses of thyroid replacement therapy will be eligible.

 11. Presence of malignancy or history of any cancer except skin cancer within the past 5
 years.

 12. Pregnancy or lactation. Premenopausal women will be requested to use birth control
 methods throughout the study and provided educational materials about the risks of
 using the study medications during pregnancy.

 13. Unable to obtain quantifiable carotid measure during screening examination.

 14. Concomitant long term use of cyclosporins (Sandimmune), macrolide antibiotics
 (erythromycin -many generic and brand name forms, clarithromycin, Biaxin, and
 Zithromax), azole antifungals (itraconazole-Sporanox, ritonavir, Norvir, and
 nelfinavir (Viracept).

 15. Orthostatic hypotension as defined by the following:

 1. The individual has a measured fall of >20 mmHg in systolic BP upon standing
 associated with symptoms lasting more than one minute (or severe symptoms that
 would not allow further lowering of BP)

 2. The standing systolic blood pressure is less than 90 mm.

 16. Triglyceride level >350 mg/dl.

 17. Severe aortic stenosis with valve area <=1.0 square cm.