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Women and men with type 2 diabetes and heart disease have similar long-term cardiovascular outcomes when receiving intensive medical therapy regardless of whether it is supplemented by revascularization. But women fare worse in quality of life, with persistent angina and lower functional status, according to a substudy of the BARI 2D trial scheduled to be published online ahead of print in the Journal of the American College of Cardiology.

In BARI 2D, 2,368 patients with type 2 diabetes and stable heart disease were randomized to intensive medical therapy with or without prompt revascularization and to receive either insulin-sensitization or insulin-provision therapy. At 5 years, rates of the primary outcome of all-cause death as well as MACE were similar between the 2 arms for both randomized strategies.

For the substudy, investigators led by Jacqueline E. Tamis-Holland, MD, of St. Luke’s-Roosevelt Hospital Center (New York, NY), compared the outcomes of women (n = 702) vs. men (n = 1,666).

At 5 years, Kaplan-Meier rates of the primary endpoint, the composite of death, MI, and stroke, and subsequent revascularization, were similar between the sexes. Women were more likely to experience congestive heart failure, although after adjustment for baseline variables the difference disappeared (HR 1.19; 99% CI 0.87-1.63; P = 0.15; table 1).

Table 1. Cumulative Outcomes at 5 Years

 
Women, though, were more likely than men to report angina, a finding which remained even after adjustment for baseline status and other confounders (adjusted OR 1.51; 99% CI 1.21-1.89; P  < 0.0001). Women also reported lower scores on the Duke Activity Status Index after adjustment (DASI; adjusted beta coefficient -1.58; 99% CI -2.84 to -0.32; P < 0.01). Meanwhile, no difference was seen in self-rated health (adjusted beta coefficient 0.32; 99% CI -2.4 to 1.7; P = 0.70).

For the most part, both sexes received the same medications (including antiplatelet therapies, statins, ACE inhibitors or ARBs, beta-blockers or calcium channel blockers) and life-style-management advice. However, a larger proportion of women were treated with nonsublingual nitrates and diuretics.

The authors point out that physical functioning can be influenced by multiple psychosocial factors, and women with CAD have been shown to have more depression and less social support than men. Thus, they write, “a more aggressive approach to the assessment and management of physical and psychosocial barriers in patients with CAD (including referral to structured cardiac rehabilitation programs, depression screening and treatment, and programs designed to aid in social support) may contribute to an improvement in functional status in women.”

Substantial Baseline Differences

The male and female cohorts differed with regard to numerous baseline demographic and clinical variables.

Compared with men, women had a longer duration of diabetes and a higher prevalence of hypertension. In addition, they had a higher mean BMI and were less likely to have an LDL level below 100 mg/dL or a hemoglobin A1c level below 7.0%. Moreover, a larger percentage of women had unstable angina or angina equivalents.

On the other hand, angiographically women’s CAD was less severe, with fewer significant lesions and total occlusions, a lower mean myocardial jeopardy index, less multiregional disease, and less ventricular dysfunction (all P < 0.01).

Interestingly, women had more baseline angina than men despite less extensive disease on angiography, the authors write, possibly attributable to endothelial dysfunction. This may cause Syndrome X, they note, “which is defined as typical angina in the setting of normal coronary angiograms . . . and is more common in women.”

Women at a Disadvantage from the Outset

“It’s good to know that the hard endpoints were similar between men and women, Om P. Ganda, MD, of the Joslin Diabetes Center (Boston, MA), told TCTMD in a telephone interview. With regard to women’s poorer quality of life, he suggested that delayed CAD presentation due to nonspecific symptoms and differences in baseline characteristics were likely responsible.

“I was struck by the fact that significantly fewer women achieved good diabetes control,” as evidenced by failure to meet goals for LDL cholesterol and hemoglobin A1c, Dr. Ganda said. Appropriate medication prescription is not enough, he emphasized; it must be accompanied by education and assistance in overcoming barriers to adherence.

The women’s reduced physical function is in part related to the persistence of angina, Dr. Ganda said. Even if women have fewer lesions, they tend to have more extensive, diffuse disease, which results in exertional intolerance, he noted. Moreover, studies have shown that obese women tend to develop myocardial dysfunction that is not explained by coronary artery blockages, he added.

Dr. Ganda agreed with the authors that more screening of women for depression and psychosocial disadvantages would be helpful. Another clinical change that could benefit women, he suggested, would be choosing CABG for multivessel disease if revascularization is warranted, as recent data from trials like FREEDOM (Farkouh ME, et al. N Engl J Med. 2012;367:2375-2384) indicate. In the current study, he pointed out, two-thirds of the women with that disease pattern undergoing revascularization received PCI.

 

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Source:
Tamis-Holland JE, Lu J, Korytkowski M, et al. 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 BARI 2D. J Am Coll Cardiol. 2013;Epub ahead of print.

 

• Drs. Tamis-Holland and Ganda report no relevant conflicts of interest.

 

Related Stories:

• Revascularization, Medical Therapy Yield Similar Mortality, MACE in Diabetic Patients with CAD
• BARI 2D: Prompt Revascularization Improves Angina Symptoms in Diabetics
• BARI 2D: Older Age Makes No Difference in Therapies for Diabetics with Stable CAD