Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial.
BACKGROUND
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.


METHODS
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.


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


METHODS
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 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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00047424.
Howard
Barbara V
BV
MedStar Research Institute, 6495 New Hampshire Ave, Suite 201, Hyattsville, MD 20783, USA. barbara.v.howard@medstar.net
Roman
Mary J
MJ
Devereux
Richard B
RB
Fleg
Jerome L
JL
Galloway
James M
JM
Henderson
Jeffrey A
JA
Howard
Wm James
WJ
Lee
Elisa T
ET
Mete
Mihriye
M
Poolaw
Bryce
B
Ratner
Robert E
RE
Russell
Marie
M
Silverman
Angela
A
Stylianou
Mario
M
Umans
Jason G
JG
Wang
Wenyu
W
Weir
Matthew R
MR
Weissman
Neil J
NJ
Wilson
Charlton
C
Yeh
Fawn
F
Zhu
Jianhui
J
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000208:ethnology / Q000209:etiology* / Q000517:prevention & control*; D001794:Blood Pressure; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000208:ethnology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000000981:diagnostic imaging; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D014463:Ultrasonography
D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents