Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes

Background: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. Methods: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. Results: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). Conclusions: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.