Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes - The SANDS randomized trial

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 ( 128130) 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 mm(2) vs 1.05 mm(2); 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.