Background: Among patients with diabetes mellitus (diabetes) and chronic coronary disease (CCD), it is unclear if invasive management improves outcomes when added to medical therapy. Methods: The ISCHEMIA Trials (ISCHEMIA and ISCHEMIA CKD) randomized CCD 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, HbA1c =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 vs. without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease [CAD] severity or left ventricular function). Results: Of 5,900 participants with complete baseline data, the median age was 64 years interquartile range (IQR) [57-70], 24% were female, and the median estimated glomerular filtration was 80 ml/min/1.732 IQR [64-95]. Among the 2,553 (43%) of participants with diabetes, median percent hemoglobin A1c was 7% IQR [7-8%], and 30% were insulin treated. Participants with diabetes had a 49% increased hazard of death or MI (HR 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 vs. without diabetes - 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 vs. without diabetes, or for clinical (female sex or insulin use) or anatomic features (CAD severity or left ventricular function) of patients with diabetes. Conclusions: Despite higher risk for death or MI, CCD patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT01471522.
View details for DOI 10.1161/CIRCULATIONAHA.121.054439
View details for PubMedID 34521217