Early Versus Delayed Invasive Management of Female Patients With Non-ST-Elevation Acute Coronary Syndrome: An Individual Patient Data Meta-Analysis

BACKGROUND: Female patients are at greater risk of adverse events following non-ST-elevation acute coronary syndrome but less frequently receive guideline-recommended coronary angiography and revascularization. Routine invasive management benefits high-risk patients, but evidence informing the optimal timing of angiography specifically in female patients is lacking. METHODS: Medline, Web of Science, and Scopus were searched up to November 2023. Randomized controlled trials investigating early versus delayed timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome were included. Individual patient data from female patients were extracted. The primary end point was a composite of all-cause mortality or myocardial infarction at 6 months. We performed a 1-stage individual patient data meta-analysis using random-effects Cox models. RESULTS: Six trials contributed individual patient data from 2257 female patients. Median time to coronary angiography was 5 hours in the early invasive group (n=1141) and 49 hours in the delayed invasive group (n=1116). Overall, there was no significant reduction in the risk of the primary end point in the early invasive group compared with the delayed group (hazard ratio, 0.79 [95% CI, 0.60-1.06]; P=0.12). Early invasive management was associated with a reduction in recurrent ischemia (hazard ratio, 0.60 [95% CI, 0.39-0.94]; P=0.025). In the prespecified subgroup analysis, high-risk female patients with Global Registry of Acute Coronary Events score >140 receiving early invasive management experienced a significantly reduced hazard for all-cause mortality or myocardial infarction at 6 months (hazard ratio, 0.65 [95% CI, 0.45-0.94]; P=0.021; Pinteraction=0.035). Similar benefits were observed for female patients with elevated cardiac biomarkers. CONCLUSIONS: Early invasive management in female patients with non-ST-elevation acute coronary syndrome, compared with delayed invasive management, was not associated with a significant reduction in the hazard for the primary end point. In prespecified subgroup analysis, high-risk female patients as assessed with Global Registry of Acute Coronary Events score >140 or elevated cardiac biomarkers experienced significant reductions in all-cause mortality or myocardial infarction at 6 months following early invasive management.