Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis.
OBJECTIVE
This study investigated the hypothesis that baseline calcified coronary atherosclerosis may determine cardiovascular disease events in response to intensive glycemic control within the Veterans Affairs Diabetes Trial (VADT).


METHODS
At baseline, 301 type 2 diabetic participants in the VADT, a randomized trial comparing the effects of intensive versus standard glucose lowering on cardiovascular events, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular end points.


RESULTS
During a median follow-up duration of 5.2 years, 89 cardiovascular events occurred. Although intensive glucose-lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC, as indicated by significant P values for treatment by log(CAC + 1) interaction terms in unadjusted and multivariable-adjusted models (0.01 and 0.03, respectively). Multivariable-adjusted hazard ratios (HRs) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories: those above and below an Agatston score of 100. Among those randomized to intensive treatment, for the subgroup with CAC >100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC < or = 100 had an event. The multivariable HR for intensive treatment for those with CAC >100 was 0.74 (95% CI 0.46-1.20; P = 0.21), while for the subgroup with CAC < or = 100, the corresponding HR was 0.08 (0.008-0.77; P = 0.03), with event rates of 39 and 4 per 1,000 person-years, respectively.


CONCLUSIONS
These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis.
Reaven
Peter D
PD
Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA. peter.reaven@va.gov
Moritz
Thomas E
TE
Schwenke
Dawn C
DC
Anderson
Robert J
RJ
Criqui
Michael
M
Detrano
Robert
R
Emanuele
Nicholas
N
Kayshap
Moti
M
Marks
Jennifer
J
Mudaliar
Sunder
S
Harsha Rao
R
R
Shah
Jayendra H
JH
Goldman
Steven
S
Reda
Domenic J
DJ
McCarren
Madeline
M
Abraira
Carlos
C
Duckworth
William
W
D017668:Age of Onset; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002114:Calcinosis / Q000473:pathology*; D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011897:Random Allocation; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs
D002118:Calcium; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents