Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial

Abstract

Background: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.

Methods and results: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions.

Conclusions: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial.

Registration: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

Keywords: coronary artery disease; ischemic heart disease; sex differences; women's health.

Figure 1. Unadjusted cumulative incidence plot of revascularization by sex, excluding revascularization for a suspected primary end point event.

A, Invasive strategy. B, Conservative strategy. Note that revascularization prompted by a suspected end point event is not included.

Figure 2. Sex differences in management and outcomes of patients with chronic coronary disease in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.

*No sex differences in revascularization rates when stratified by number of vessels diseased on coronary angiography, invasive group. **Revascularization in 72.3% of those undergoing catheterization in conservative group among women, 82.3% among men (P=0.007). ***The primary composite outcome included cardiovascular death, myocardial infarction, hospitalization for heart failure, unstable angina, or resuscitated cardiac arrest. The use of invasive procedures, medical therapy goal attainment, and the primary outcome event rate were compared by participant sex in the ISCHEMIA trial. The use of cardiac catheterization was similar for women and men in both the routine invasive strategy group and the conservative strategy group. The rate was far lower in the conservative strategy group in which catheterization was reserved for failure of medical therapy. The rate of revascularization was far lower for women in the invasive group. However, there was no sex difference in revascularization after stratifying for the lower number of vessels diseased on coronary angiography in women (see Table 2 for details). In the conservative strategy group, overall revascularization rates were similar, but among those who had catheterization, revascularization was lower among women (**). Women were less likely to reach the low‐density lipoprotein (LDL) and systolic blood pressure (SBP) treatment goals. The primary outcome event rate was similar for women and men. HR indicates hazard ratio. Created with BioRender.com.

Figure 3. Unadjusted cumulative incidence plot of trial primary and major secondary outcomes and all‐cause mortality by sex.

A, Cardiovascular death, myocardial infarction (MI), hospitalization for unstable angina or heart failure, or resuscitated cardiac arrest. B, Cardiovascular death or MI. C, All‐cause death.