Sex Differences in Coronary Disease Health Status Outcomes: the ISCHEMIA Trial

BACKGROUND: In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, women had worse angina than men despite less severe coronary artery disease (CAD) and ischemia. We examined which patient and treatment factors might explain sex-based differences in angina. METHODS: ISCHEMIA randomized patients with moderate or severe ischemia to an initial invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with invasive management reserved for GDMT failure. Coronary CT angiography was performed in most participants. Angina-related health status was collected at baseline and 1-year using the Seattle Angina Questionnaire (SAQ). RESULTS: Of 4,617 ISCHEMIA participants with complete SAQ data, women averaged 6.5 points (95% CI 5.2-7.8) lower (worse) baseline SAQ summary scores (SS) than men. This difference was not reduced by adjustment for demographics and clinical characteristics. Women had lower unadjusted 1-year SAQ-SS than men (Invasive -3.8 points, Conservative -5.7 points). These sex-based differences were attenuated but not eliminated by adjustment for baseline SAQ-SS. Adjustment for post-randomization treatment (GDMT intensity, risk factor goal achievement and, in the invasive strategy, complete revascularization) did not narrow the sex difference. CONCLUSIONS: Women with chronic CAD in ISCHEMIA had worse angina-related health status than men at baseline and 1-year. Differences were not explained by demographic or clinical characteristics, intensity of GDMT, or completeness of revascularization. It is thus important to consider other factors that may mediate these results, including differences in nociception, coronary microvascular dysfunction and/or vasospasm.