Increased hazard of myocardial infarction with insulin-provision therapy in actively smoking patients with diabetes mellitus and stable ischemic heart disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial

Asrar A. Khan, Matthew J. Chung, Eric Novak, David L. Brown

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background--In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (IP) therapy, as opposed to insulin sensitization (IS) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (MI). Methods and Results--We analyzed BARI 2D patients who were active smokers randomized to IP or IS therapy. The primary end point was fatal or nonfatal MI. PAI-1 (plasminogen activator inhibitor 1) activity was analyzed at 1, 3, and 5 years. Of 295 active smokers, MI occurred in 15.4% randomized to IP and in 6.8% randomized to IS over the 5.3 years (P=0.023). IP therapy was associated with a 3.2-fold increase in the hazard of MI compared with IS therapy (hazard ratio: 3.23; 95% confidence interval, 1.43- 7.28; P=0.005). Baseline PAI-1 activity (19.0 versus 17.5 Au/mL, P=0.70) was similar in actively smoking patients randomized to IP or IS therapy. However, IP therapy resulted in significantly increased PAI-1 activity at 1 year (23.0 versus 16.0 Au/mL, P=0.001), 3 years (24.0 versus 18.0 Au/mL, P=0.049), and 5 years (29.0 versus 15.0 Au/mL, P=0.004) compared with IS therapy. Conclusions--Among diabetic patients with stable ischemic heart disease who were actively smoking, IP therapy was independently associated with a significantly increased hazard of MI. This finding may be explained by higher PAI-1 activity in active smokers treated with IP therapy.

Original languageEnglish (US)
Article numbere005946
JournalJournal of the American Heart Association
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2017

Keywords

  • Coronary artery disease
  • Diabetes mellitus
  • Insulin
  • Myocardial infarction
  • Smoking

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