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“Our results highlight a need to be extra attentive to risk-factor modification among women,” says Harmony Reynolds, MD.

Women with chronic coronary disease experienced similar risk-adjusted outcomes to men, even as they attained risk-factor modification goals less frequently and had less extensive artery disease, according to findings from a secondary analysis of the ISCHEMIA trial published in the Journal of the American Heart Association.

“Many studies show key sex differences in cardiovascular disease,” Dr. Harmony Reynolds, MD, says. “We wondered how those would sum up in our ISCHEMIA trial cohort that was so carefully phenotyped. In myocardial infarction, it’s well documented that women have poorer outcomes than men. Depending on the study, one may or may not be able to explain that through differences in demographics among women, their treatment, and so on. But in the chronic coronary disease literature, it has seemed that women have very similar outcomes to men.”

Women who have chronic coronary disease tend to be older than men with the condition and have more comorbidities. However, they also experience less atherosclerosis compared with men, the researchers explain.

In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, researchers randomly assigned patients with moderate-to-severe ischemia to receive either invasive management, consisting of guideline-directed medical therapy and interventions such as angiography and revascularization, or to receive conservative management, defined as guideline-directed medical therapy alone. In this analysis, Dr. Reynolds and colleagues evaluated the study’s main outcome, defined as cardiovascular-related death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, for all study participants by sex. The study included 1,168 women (22.6%) and 4,011 men (77.4%).

Women assigned to the invasive group underwent revascularization at a rate of 73.4%, compared with 81.2% of men assigned to the same group, Dr. Reynolds and colleagues write (P<0.001). This difference occurred even though men and women in this group received cardiac catheterization at similar rates, they noted.

The researchers report that women had less extensive disease. Three-quarters of men (74.8%) assigned to the invasive group had multivessel coronary artery disease, compared with just 60% of women assigned to invasive therapy. Furthermore, 12.3% of women had stenosis of less than 50%, versus only 4.5% of men.

Four-year catheterization rates were similar for men and women assigned to the conservative therapy group, the researchers wrote. About one-quarter of both women (26.3%) and men (25.6%) underwent catheterization in the conservative treatment group.

Dr. Reynolds and colleagues reported no significant differences between sexes in the primary outcome of cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest (HR=0.93, 95% CI, 0.77–1.13; P=0.47 for women compared with men). The same was true for one of the major secondary outcomes, cardiovascular death or myocardial infarction (adjusted HR for women vs men = 0.93; 95% CI, 0.76–1.14; P=0.49).

However, the researchers found that guideline-directed medical therapy usage among women was lower than that of men, and women achieved fewer goals in mitigating risk factors than male patients. Women were less likely than men to achieve their goals of reaching a systolic blood pressure below 140 mm Hg and an LDL-cholesterol level below 70 mg/dL and were also less likely to use aspirin.

Interpreting the Data

“All we can do is speculate,” says Dr. Reynolds of the possible causes of these differences in treatment. “When we look at the variables we have available, it’s not immediately apparent why women get less treatment. In some cases, these are modest differences, yet they may be important.”

She points to her team’s data on aspirin use as an example: 94.7% of women in the study received aspirin or an alternative at baseline, compared with 96.6% of men. That difference may seem small.

“But that is a particularly important medical therapy variable for us,” Dr. Reynolds says.

The gap in cholesterol goals is significantly greater: women achieved their cholesterol goals 49.5% of the time, whereas men achieved the same goal 60.5% of the time, Reynolds adds, describing the gap as “concerning.” This difference held even as statin prescriptions roughly doubled for both sexes throughout the study.

“Our results highlight a need to be extra attentive to risk-factor modification among women,” Reynolds says. “We need to be super attentive to our women and make sure they’re getting all the medications they need.”