Abstract 15284: The Impact of Insulin Provision vs. Insulin Sensitization Therapy on the Risk of Myocardial Infarction in Diabetic Smokers With Stable Ischemic Heart Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Introduction: In the Bypass Angioplasty Revascularization 2 Diabetes (BARI 2D) trial, randomization of diabetic patients with stable ischemic heart disease (SIHD) to insulin provision (IP), as opposed to insulin sensitization (IS), resulted in biochemical evidence of a prothrombotic effect but no increase in adverse clinical outcomes. We hypothesized that the combination of the prothrombotic effects of IP therapy in combination with the prothrombotic state induced by smoking would result in an increased risk of coronary thrombosis manifested by myocardial infarction (MI).
Methods: We analyzed BARI 2D patients with SIHD and diabetes mellitus who were actively smoking at baseline, randomized to IP or IS therapy and followed for an average of 5.3 years. The primary end point was MI. We used multivariate Cox regression analysis to evaluate the independent effect of IP on MI among current smokers. Plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were assayed at baseline and at 1, 3 and 5 years of follow-up.
Results: Of the 2360 patients with known smoking status, 295 were active smokers at baseline. Among active smokers, 76% were male, 65% were white and the mean age was 57 years. MI occurred in 11% of smokers over the 5-year follow-up. Randomization of smokers to IP therapy was associated with a 2.8-fold increase in the hazard of MI compared to randomization to IS (Hazard Ratio (HR)=2.84; 95% Confidence Interval (CI):1.23-6.52; P=0.014). Baseline PAI-1 activity (17.5 vs. 19.0 Au/ml, P=0.70) and antigen values (26.0 vs. 25.5 ng/ml, P=0.76) were similar in patients randomized to IS or IP. However, IP was associated with significantly increased PAI-1 activity and antigen levels at 1 (23.0 vs. 16.0 Au/ml, P=0.001 and 33.0 vs. 22.5 ng/ml, P=0.003), 3 (24.0 vs. 18.0 Au/ml, P=0.049 and 31.0 vs. 24.0 ng/ml, P=0.008) and 5 years (29.0 vs. 15.0 Au/ml, P=0.004 and 37.0 vs. 23.0 ng/ml, P=0.003) compared to IS.
Conclusion: Among diabetics with SIHD, the combination of smoking and IP therapy is associated with a significantly increased risk in MI. This finding may be explained by higher PAI-1 activity and antigen levels in smokers treated with IP. If confirmed in larger randomized clinical trials, diabetic smokers with SIHD should be treated with IS rather than IP therapy.
- Diabetes (Type II)
- Tobacco and electronic cigarettes
- Inflammation and inflammatory markers
- Acute coronary syndromes
Author Disclosures: A.A. Khan: None. M.J. Chung: None. E. Novak: None. D.L. Brown: None.
- © 2016 by American Heart Association, Inc.