Impact of Coronary Artery Disease on Cardiovascular Outcomes Differs Between Men and Women With Severe Aortic Stenosis

BACKGROUND: There is heterogeneity in coronary artery disease (CAD) severity among individuals with severe aortic stenosis (AS), but whether this differentially influences prognosis is unknown. METHODS: Patients with severe AS in the PARTNER 1, 2, and 3 trials and registries (Placement of Aortic Transcatheter Valves) were stratified by obstructive CAD (coronary stenosis ≥50%, prior myocardial infarction, or revascularization) or no obstructive CAD (all stenoses <50%). Multivariable Cox proportional-hazards models examined the association between CAD severity groups and clinical outcomes. The primary composite end point was death, heart failure hospitalization, or stroke at 5 years. Interaction between sex and CAD severity was evaluated. RESULTS: Among 7505 patients with severe AS, 2062 (27.5%) had no obstructive CAD and were more likely to be women (60.5%) with fewer CAD risk factors. After multivariable adjustment, the primary end point was significantly lower among patients with no obstructive CAD compared with those with obstructive CAD (adjusted hazard ratio, 0.92 [CI, 0.84–1.00]; P =0.04), irrespective of AS treatment. However, there were significant differences by sex ( P interaction =0.0002). Men with no obstructive CAD had a 16% lower event rate compared with men with obstructive CAD (adjusted hazard ratio, 0.84 [CI, 0.73–0.96]; P =0.01). In contrast, women with no obstructive CAD did not have a significantly lower rate of death, stroke, or heart failure hospitalization compared with women with obstructive CAD (adjusted hazard ratio, 0.95 [CI, 0.85–1.07]; P =0.41). Women with no obstructive CAD had a more advanced heart failure phenotype and higher event rates compared with men with no obstructive CAD. CONCLUSIONS: Obstructive CAD was associated with a higher risk of long-term adverse events after treatment for severe AS, but there was a significant sex disparity in clinical outcomes among men and women with no obstructive CAD. Further study is needed to optimize the evaluation and management of women with severe AS.