Title: Stop Atherosclerosis in Native Diabetics Study (SANDS)
Trial Sponsor: National Heart, Lung, and Blood Institute and the National Institutes of Health
Year Published 2008
Topic(s): General Cardiology
Summary Posted: 4/10/2008
Writer: Anthony A. Bavry, M.D., M.P.H.
Author Disclosure: Consulting Fees/Honoraria: Boston Scientific, Modest (< $10,000); Consulting Fees/Honoraria: Access Closure, Modest (< $10,000)
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Sanofi Aventis, Significant (>= $10,000); Research/Research Grants: Heartscape, Significant (>= $10,000); Research/Research Grants: Eisai, Significant (>= $10,000); Research/Research Grants: Ethicon, Significant (>= $10,000); Research/Research Grants: Bristol Myers Squibb, Significant (>= $10,000); Research/Research Grants: The Medicines Company, Significant (>= $10,000)
Description
The goal of the trial was to evaluate a strategy of aggressive lipid and blood pressure lowering compared with standard therapy in type 2 diabetic patients without baseline cardiovascular disease.
Hypothesis
Aggressive lipid and blood pressure lowering will be more effective in preventing the progression of atherosclerosis measured by common carotid artery intimal medial thickness.
Drugs/Procedures Used
Type 2 diabetic patients were randomized to a strategy of aggressive lipid (low-density lipoprotein [LDL] cholesterol =70 mg/dl) and blood pressure lowering (systolic blood pressure [SBP] =115 mm Hg) (n = 252) or standard therapy (LDL =100 mg/dl and SBP =130 mm Hg) (n = 247).
Concomitant Medications
At baseline, the use of insulin plus oral hypoglycemics was 91% versus 79% (p = 0.002) and aspirin was 70% versus 69% (p = 0.74), for aggressive versus standard therapy.
Principal Findings
At baseline, the mean body mass index was 34 kg/m2, mean glycated hemoglobin was 8.1%, and mean duration of diabetes was 9.2 years (in the aggressive group). At 3 years, LDL cholesterol decreased from 104 to 72 mg/dl and SBP decreased from 128 to 117 mm Hg in the aggressive therapy group. In the standard therapy group, LDL cholesterol remained at 104 mg/dl and SBP decreased from 133 to 129 mm Hg.

The carotid intimal media thickness decreased 0.012 mm in the aggressive therapy group and increased 0.038 mm in the standard therapy group (p < 0.001) at 36 months. Left ventricular mass decreased by 8 g versus decreased by 3.3 g (p = 0.02), and left ventricular mass index decreased by 2.4 g/m2 versus decreased by 1.2 g/m2 (p = 0.03), respectively.

Primary cardiovascular events occurred in 1.5% of the aggressive therapy group and 1.1% of the standard therapy group (p = 0.51). Adverse events related to lipid drugs were 18.3% versus 14.2% (p = 0.22) and adverse events related to blood pressure medication drugs were 26.6% versus 15.4% (p = 0.002), respectively.
Interpretation
Among Native American patients with type 2 diabetes, aggressive lipid and blood pressure lowering is beneficial at preventing the progression of carotid atherosclerosis. In this population, reduction of LDL cholesterol to a mean of 72 mg/dl and SBP to a mean of 117 mm Hg regressed carotid artery intimal media thickness at 3 years of follow-up, compared with less stringent risk factor modification. This contrasted with progression of carotid atherosclerosis in the standard therapy group. Left ventricular mass and mass index also regressed more with aggressive therapy.

Primary cardiovascular events were infrequent and occurred at a similar rate in both groups. Adverse events from blood pressure medications (hypotension, hyperkalemia) were more frequent in the aggressive group.

Several important caveats need to be pointed out. First, some caution should be exercised in extrapolating these results to non-Native American diabetic patients. Second, the primary outcome of this trial was a surrogate endpoint; therefore, the combined effect of aggressive lipid and blood pressure lowering on primary prevention of cardiovascular events in type 2 diabetics remains unknown. The accompanying editorial suggests that one interpretation of the trial would be to aggressively treat with lipids in these patients, which is supported by other studies, while awaiting the results of the ACCORD and SPRINT trials to help guide blood pressure management.
Conditions
• Diabetes mellitus

Therapies
• Lipid-lowering agent
• Medical

Study Design
Randomized. Blinded.

Patients Screened: 1,067
Patients Enrolled: 548
Mean Follow-Up: 3 years
Mean Patient Age: 55
% Female: 66

Primary Endpoints
Change in common carotid artery intimal media thickness
Secondary Endpoints
• Adverse cardiovascular events
• Adverse events due to medications
• Carotid artery cross-sectional area (mm2), plaque score (0-8), plaque (%)
• Left ventricular mass (g), left ventricular mass index (g/m2)
• Ejection fraction (%)
Patient Population
• Native Americans with type 2 diabetes
• LDL cholesterol of at least 100 mg/dl
• SBP of at least 130 mm Hg
Exclusions:
• Baseline cardiovascular disease
• New York Heart Association III or IV heart failure
• Liver transaminase levels more than twice the upper limit of normal
• Primary hyperlipidemia or hypercholesterolemia due to hyperthyroidism
• Nephrotic syndrome
References: Howard BV, Roman MJ, Devereaux RB, et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes. JAMA 2008;299:1678-1689.