Cardiovascular Disease, Carotid Atherosclerosis, Diabetes, Hyperlipidemia, Hypertension
Conditions
Keywords
lowering LDL and BP below current targets, LDL cholesterol treatment, blood pressure treatment, carotid intimal medial thickness, prevent progression of CVD
Brief summary
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.
Detailed description
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.
Interventions
DRUGFDA approved drugs to treat blood pressure and cholesterol
Sponsors
Cynthia West
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changing LDL Cholesterol | 36 months | LDL cholesterol intervention to lower targets than are currently recommended to retard atherosclerosis measured by LDL-C mg/dL. Scale: LDL cholesterol levels should be less than 100 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changing Blood Pressure | 36 month follow-up | Treatment of blood pressure to prevent/reduce diseases of heart and blood vessels. Measured by mmHG. Normal values should be below 120/80 mm Hg. |
Countries
United States
Participant flow
Recruitment details
Participants were identified from the local Indian hospital service center, or DM clinic. In March 2004, the DSMB recommended and the SC voted to over-recruit by 10-20% to compensate for the possible need for more aggressive treatment for participants with baseline CVD. Randomization concluded in July 2004 with 547 randomized participants.
Pre-assignment details
Sonogram eligibility was confirmed by tape review at the core lab prior to randomization. A potential participant had to have LDL-C \> 100 mg/dL and systolic BP \> 130/85 mmHg. A participant could undergo a maximum of four screening visits within a 3-month period to confirm eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment standard targets of LDL-C \< 100 mg/dL and BP \< 130/85 mm Hg | 247 |
| Aggressive Treatment /aggressive targets of LDL-C \< 70 mg/dL plus BP \< 115/75 mm Hg | 252 |
| Total | 499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Recruitment and Enrollment | change in treatment guidelines | 24 | 25 |
Baseline characteristics
| Characteristic | Standard Treatment | Aggressive Treatment | Total |
|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 4.24 | 55.3 years STANDARD_DEVIATION 4.24 | 56.1 years STANDARD_DEVIATION 4.24 |
| Sex: Female, Male Female | 163 Participants | 164 Participants | 327 Participants |
| Sex: Female, Male Male | 84 Participants | 88 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 247 | 0 / 252 |
| serious Total, serious adverse events | 1 / 247 | 4 / 252 |
Outcome results
Primary
Changing LDL Cholesterol
LDL cholesterol intervention to lower targets than are currently recommended to retard atherosclerosis measured by LDL-C mg/dL. Scale: LDL cholesterol levels should be less than 100 mg/dL
Time frame: 36 months
Population: Native American
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Standard Treatment | Changing LDL Cholesterol | 100 Mg/dl | Standard Deviation 74 |
| Aggressive Treatment | Changing LDL Cholesterol | 70 Mg/dl | Standard Deviation 91 |
Secondary
Changing Blood Pressure
Treatment of blood pressure to prevent/reduce diseases of heart and blood vessels. Measured by mmHG. Normal values should be below 120/80 mm Hg.
Time frame: 36 month follow-up
Population: American Indian
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Treatment | Changing Blood Pressure | 130 mm Hg | Standard Deviation 0.001 |
| Aggressive Treatment | Changing Blood Pressure | 115 mm Hg | Standard Deviation 0.001 |