BACKGROUND: Among patients with diabetes and chronic coronary disease, it is unclear
if invasive management improves outcomes when added to medical therapy. METHODS: The
ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and
Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized
chronic coronary disease patients to an invasive (medical therapy + angiography and
revascularization if feasible) or a conservative approach (medical therapy alone with
revascularization if medical therapy failed). Cohorts were combined after no trial-specific
effects were observed. Diabetes was defined by history, hemoglobin A1c >= 6.5%, or
use of glucose-lowering medication. The primary outcome was all-cause death or myocardial
infarction (MI). Heterogeneity of effect of invasive management on death or MI was
evaluated using a Bayesian approach to protect against random high or low estimates
of treatment effect for patients with versus without diabetes and for diabetes subgroups
of clinical (female sex and insulin use) and anatomic features (coronary artery disease
severity or left ventricular function). RESULTS: Of 5900 participants with complete
baseline data, the median age was 64 years (interquartile range, 57-70), 24% were
female, and the median estimated glomerular filtration was 80 mL.min(-1.)1.73(-2)
(interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes,
the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were
insulin-treated. Participants with diabetes had a 49% increased hazard of death or
MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up
the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66
(95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes,
respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free
survival among participants with diabetes. Female and male patients with insulin-treated
diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56)
and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in
death or MI between strategies for patients with diabetes versus without diabetes,
or for clinical (female sex or insulin use) or anatomic features (coronary artery
disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS:
Despite higher risk for death or MI, chronic coronary disease patients with diabetes
did not derive incremental benefit from routine invasive management compared with
initial medical therapy alone.
