Impact of the 2023 ACR/EULAR classification criteria on thrombotic antiphospholipid syndrome: reclassification patterns and long-term outcomes in a 419-patient cohort

The 2023 ACR/EULAR classification criteria for antiphospholipid syndrome (APS) were developed to improve specificity and to define more homogeneous research populations. However, their performance in real-world cohorts of thrombotic APS with long-term hard outcomes remains insufficiently characterized. We aimed to apply the 2023 ACR/EULAR criteria to a large, single-center cohort of patients with Sydney-classified thrombotic APS and to assess whether classification status is associated with clinical phenotype, antithrombotic treatment exposure, and long-term outcomes. We conducted a retrospective observational study including 419 patients with thrombotic APS fulfilling the 2006 Sydney classification criteria and followed at a tertiary referral center in northern Spain between 1993 and 2025. The 2023 ACR/EULAR classification criteria were retrospectively applied to all patients at APS diagnosis using the qualifying clinical event and the corresponding aPL profile within the required temporal window. Demographic data, cardiovascular and venous thromboembolic risk factors, clinical and serological domains, treatment exposure, recurrent thrombosis, major bleeding, cumulative damage, and all-cause mortality were collected. Comparisons were performed between patients who fulfilled and those who did not fulfill the new criteria. Overall, 239 patients (57.0%) fulfilled the 2023 ACR/EULAR criteria. Median follow-up was 5.0 years [IQR 3.1–9.3]. Classified patients were younger, less frequently female, and had fewer competing cardiovascular and venous thromboembolic risk factors. Persistent lupus anticoagulant positivity and high IgG anticardiolipin and/or anti-β2-glycoprotein I profiles were more frequent among classified patients, whereas moderate/high IgM profiles were more common among non-classified patients. Recurrent thrombosis occurred in 67 patients (16.0%), with similar incidence rates among patients fulfilling and not fulfilling the 2023 ACR/EULAR criteria (2.44 [95% CI 1.77–3.28] vs. 2.41 [95% CI 1.52–3.61] per 100 patient-years; p = 0.99). Adjusted time-to-event analyses did not identify significant differences in recurrent thrombosis or all-cause mortality according to classification status, whereas major bleeding-free probability was higher among patients fulfilling the 2023 ACR/EULAR criteria. Cumulative DIAPS scores were similar between groups. Anticoagulant therapy was prescribed in 299 patients (71.4%), with similar exposure in both groups. In this large real-world cohort of thrombotic APS, the 2023 ACR/EULAR criteria identified a more specific APS phenotype but excluded a substantial proportion of Sydney-classified patients with clinically relevant thrombotic burden. Classification status was not independently associated with recurrent thrombosis or mortality, although adjusted major bleeding-free probability was higher among classified patients. These findings reinforce the role of the 2023 criteria as a tool for research standardization and emphasize that they should not be equated with diagnosis or used in isolation to guide individualized management decisions.