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The SANDS Randomized Trial

Barbara V. Howard, PhD; Mary J. Roman, MD; Richard B. Devereux, MD; Jerome L. Fleg, MD; James M. Galloway, MD; Jeffrey A. Henderson, MD, MPH; Wm. James Howard, MD; Elisa T. Lee, PhD; Mihriye Mete, PhD; Bryce Poolaw, MD; Robert E. Ratner, MD; Marie Russell, MD; Angela Silverman, MSN, CANP; Mario Stylianou, PhD; Jason G. Umans, MD, PhD; Wenyu Wang, PhD; Matthew R. Weir, MD; Neil J. Weissman, MD; Charlton Wilson, MD; Fawn Yeh, PhD; Jianhui Zhu, MD

JAMA. 2008;299(14):1678-1689.

Context  Individuals with diabetes are at increased risk for cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested.

Objective  To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower vs standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower.

Design, Setting, and Participants  A randomized, open-label, blinded-to-end point, 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events.

Interventions  Participants were randomized to aggressive (n=252) vs standard (n=247) treatment groups with stepped treatment algorithms defined for both.

Main Outcome Measures  Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness (IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events.

Results  Mean target LDL-C and SBP levels for both groups were reached and maintained. Mean (95% confidence interval) levels for LDL-C in the last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (–0.012 mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also regressed (–0.02 mm² vs 1.05 mm²; P < .001); and there was greater decrease in left ventricular mass index (–2.4 g/m^2.7 vs –1.2 g/m^2.7; P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87) did not differ significantly between groups.

Conclusions  Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.

Trial Registration  clinicaltrials.gov Identifier: NCT00047424

Author Affiliations: MedStar Research Institute, Hyattsville, Maryland (Drs B. V. Howard, Mete, Ratner, Umans, Weissman, and Zhu, and Ms Silverman); Weill Cornell Medical College, New York, New York (Drs Roman and Devereux); National Heart, Lung, and Blood Institute, Bethesda, Maryland (Drs Fleg and Stylianou); University of Arizona Health Science Center, Tucson (Dr Galloway); Black Hills Center for American Indian Health, Rapid City, South Dakota (Dr Henderson); Washington Hospital Center, Washington, DC (Dr W. J. Howard); University of Oklahoma Health Sciences Center, Oklahoma City (Drs Lee, Wang, and Yeh); Lawton Indian Hospital, Lawton, Oklahoma (Dr Poolaw); Phoenix Indian Medical Center, Phoenix, Arizona (Drs Russell and Wilson); and University of Maryland School of Medicine, Baltimore (Dr Weir).

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