Refining prediction of major bleeding on antiplatelet treatment after transient ischaemic attack or ischaemic stroke

Abstract

Introduction: Bleeding is the main safety concern of treatment with antiplatelet drugs. We aimed to refine prediction of major bleeding on antiplatelet treatment after a transient ischaemic attack (TIA) or stroke by assessing the added value of new predictors to the existing S2TOP-BLEED score. Patients and methods: We used Cox regression analysis to study the association between candidate predictors and major bleeding among 2072 patients with a transient ischaemic attack or ischaemic stroke included in a population-based study (Oxford Vascular Study – OXVASC). An updated model was proposed and validated in 1094 patients with a myocardial infarction included in OXVASC. Models were compared with c-statistics, calibration plots, and net reclassification improvement. Results: Independent predictors for major bleeding on top of S2TOP-BLEED variables were peptic ulcer (hazard ratio (HR): 1.72; 1.04–2.86), cancer (HR: 2.40; 1.57–3.68), anaemia (HR: 1.55; 0.99–2.44) and renal failure (HR: 2.20; 1.57–4.28). Addition of those variables improved discrimination from 0.69 (0.64–0.73) to 0.73 (0.69–0.78) in the TIA/stroke cohort (p = 0.01). Performance improved particularly for upper gastro-intestinal bleeds (0.70; 0.64–0.75 to 0.77; 0.72–0.82). Net reclassification improved over the entire range of the score (net reclassification improvement: 0.56; 0.36–0.76). In the validation cohort, discriminatory performance improved from 0.68 (0.62–0.74) to 0.70 (0.64–0.76). Discussion and Conclusion: Peptic ulcer, cancer, anaemia and renal failure improve predictive performance of the S2TOP-BLEED score for major bleeding after stroke. Future external validation studies will be required to confirm the value of the STOP-BLEED+ score in transient ischaemic attack/stroke patients.