Sex Differences in Presentation and Outcome Among Patients With Type 2 Diabetes and Coronary Artery Disease Treated With Contemporary Medical Therapy With or Without Prompt Revascularization: A Report From the BARI 2D Trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes)

Study Questions:

Are the gender differences in management of patients with coronary artery disease (CAD) partially explained by clinical presentation and outcomes?

Methods:

Data from the BARI 2D trial, an international multicenter randomized clinical trial that evaluated the optimal treatment for patients with diabetes mellitus and documented CAD, were used. Between January 1, 2001, and March 31, 2005, 2,368 participants were enrolled from 49 clinical sites in the United States, Canada, Brazil, Mexico, Czech Republic, and Austria. Patients were excluded if they had unstable symptoms necessitating revascularization, severe left main disease (≥50% stenosis), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) in the preceding 12 months or a history of chronic kidney disease with a serum creatinine above 2.0 mg/dl. Physicians were queried before randomization with regard to the recommended method of revascularization, and patients entered into either the PCI or CABG stratum. Patients were then randomized in a 2 x 2 factorial design to a strategy of prompt revascularization plus intensive medical therapy versus initial intensive medical therapy alone with clinically indicated revascularization for treatment of CAD. Subjects were randomly assigned to an insulin-providing or an insulin-sensitizing strategy for glycemic control. The primary endpoint of the BARI 2D trial was the rate of death from any cause. The principal secondary endpoint was a composite of death, myocardial infarction (MI), or stroke (cerebrovascular accident [CVA]) at 5 years of follow-up. Baseline variables, study interventions, and outcomes were compared between women and men randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization.

Results:

Among the 2,368 patients, 702 (29.6%) were women. A larger proportion of women were black. Compared with men, women reported longer durations of diabetes, had a higher prevalence of hypertension, and were less likely to have had a prior MI or to have ever smoked cigarettes. The mean body mass index was higher in women than men, and fewer women than men had a low-density lipoprotein <100 mg/dl and a glycated hemoglobin <7.0%. At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Women were more likely than men to have unstable angina in the 6 weeks preceding enrollment. Among patients with stable symptoms, more women than men had an unfavorable Canadian Cardiovascular Society functional class (class 3 and 4). Women had lower Duke Activity Status Index (DASI) scores and lower scores for Self-Rated Health. Over 5 years, no sex differences were observed in the BARI 2D study outcomes after adjustment for difference in baseline variables (death/MI/CVA: hazard ratio, 1.11; 99% confidence interval [CI], 0.85-1.44). However, women reported more angina than men (adjusted odds ratio, 1.51; 99% CI, 1.21-1.89; p < 0.0001) and had lower scores for the DASI (p < 0.01).

Conclusions:

The investigators concluded that no sex differences were observed for several outcomes including death, MI, or CVA among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower activity scores after 5 years of medical therapy with or without prompt revascularization.

Perspective:

These data support findings from prior studies, which have also observed greater symptoms among women despite less occlusive disease. This highlights the need for specialized interventions that reduce angina among women. The lower level of fitness among women is an important concern to be addressed; improvement in fitness may result in improved outcomes and reduction in symptoms. Further research is required to answer such questions.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Insulin, Follow-Up Studies, Czech Republic, Canada, Disease Management, Creatinine, Angioplasty, Percutaneous Coronary Intervention, Mexico, Austria, Renal Insufficiency, Brazil, Coronary Angiography, Cardiology, Coronary Artery Bypass, United States, Diabetes Mellitus


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