COURAGE Substudy: PCI Adds No Overall Benefit to OMT Alone in Either Women or Men
Women and men with stable CAD achieve similarly good results for most major outcomes regardless of whether they are treated with an initial strategy of optimal medical therapy (OMT) alone or in combination with PCI, according to subanalysis of the COURAGE study published online July 24, 2015, ahead of print in the American Heart Journal. However, PCI did appear as if it might be particularly beneficial for women in terms of MI, hospitalization for heart failure, and need for subsequent revascularization.
“After we adjusted for all the differences in treatment effect by sex for the primary endpoint, we still do not see any difference overall for PCI vs OMT between men and women,” said William E. Boden, MD, of Albany Stratton VA Medical Center (Albany, NY), in a telephone interview with TCTMD. “But this study does suggest that if we had included more women, we might have seen a PCI signal potentially emerge.”
For COURAGE, the researchers looked at outcomes in 2,287 patients (15% women and 85% men) with stable CAD who were randomized to OMT with or without PCI at multiple centers between 1999 and 2004. The main trial results, published in the New England Journal of Medicine (NEJM) in 2007, showed no advantage to adding PCI to OMT for the composite of all-cause death and nonfatal MI (primary endpoint) over a median follow-up of 4.6 years.
For the subanalysis, Dr. Boden and colleagues compared outcomes by patient sex and treatment assignment after adjustment for relevant baseline characteristics.
Some Sex-Based Disparities
Compared with men enrolled in COURAGE, women were older (64 vs 62 years old), more likely to be white and to have a family history of CAD, and less likely to have had prior revascularization. Women also had higher LVEF, fewer diseased coronary vessels, and higher baseline HDL but worse kidney function and a slightly longer duration of angina. Additionally, on the Seattle Angina Questionnaire (SAQ), both the angina-related physical limitation and the angina frequency scores indicated poorer health status at baseline in women.
At a median follow-up of 4.6 years, the treatment strategies were similarly effective for men and women with regard to the primary endpoint and to death and hospitalization for ACS. However, women appeared to benefit more from PCI than men in terms of MI, hospitalization for heart failure, and need for subsequent revascularization (table 1).
Freedom from angina at 60 months was similar in men and women regardless of treatment strategy. Importantly, SAQ angina-related physical limitation scores improved more in women than in men (P = .003). Looking at scores by treatment strategy, the OMT-alone group improved less than the added-PCI group (P = .008), but no interaction was seen between sex and treatment effect. SAQ angina frequency score improved equally for both sexes over time with either treatment, although OMT patients overall improved less than those who also received PCI.
Women Often Shortchanged
Dr. Boden explained that patient sex was 1 of 8 covariates examined in the main COURAGE trial. In the 2007 NEJM paper, the researchers reported an unadjusted hazard ratio of 0.65 (95% CI 0.40-1.06) for PCI vs OMT in women, a finding that “was really tilting strongly in favor of PCI benefit,” he noted.
The new adjusted analysis, Dr. Boden added, offers “provocative findings” that beg the question of whether there are important sex-based differences still to be elucidated. Hospitalization for heart failure, even though it was not a prespecified endpoint, is an outcome of interest because it has been shown to powerfully predict adverse outcomes in patients with stable CAD and preserved ejection fraction, he commented.
Dr. Boden and colleagues note that in “current practice, women with [stable ischemic heart disease] continue to be evaluated and treated less aggressively than men, despite the fact that the results from multiple observational studies do not justify this practice and current practice guidelines do not make any distinction in diagnostic or therapeutic recommendations based on sex.”
The present subanalysis demonstrates that when aggressive secondary prevention measures are applied, “associated outcomes in women were at least comparable, if not superior, to those observed in men,” the investigators say. However, despite women appearing to do better with PCI for some endpoints, “comparison of multiple outcomes between small subgroups limits the ability to draw causal inferences,” they caution.
The investigators add that the findings “underscore the imperative to ensure an adequate and representative recruitment of women participants in prospective, randomized trials of [stable ischemic heart disease] patients in order to more definitively explore the important potential for sex-based differences in therapeutic responses to initial management strategies.”
Acharjee S. Teo KK, Jacobs AK, et al. Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: a pre-specified subset analysis of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial. Am Heart J. 2015;Epub ahead of print.
- Gender Gap Closing for Patients Undergoing PCI
- ACS Less Aggressively Treated, More Frequently Fatal in Women
- Dr. Boden reports no relevant conflicts of interest.