Nina A Hilkens1, Ale Algra2, Hans-Christoph Diener2, Johannes B Reitsma2, Philip M Bath2, Laszlo Csiba2, Werner Hacke2, L Jaap Kappelle2, Peter J Koudstaal2, Didier Leys2, Jean-Louis Mas2, Ralph L Sacco2, Pierre Amarenco2, Leila Sissani2, Jacoba P Greving2. 1. From the Julius Center for Health Sciences and Primary Care (N.A.H., A.A., J.B.R., J.P.G.) and Department of Neurology and Neurosurgery (A.A., L.J.K.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (H.-C.D.), University Hospital Essen, Germany; Stroke Trials Unit (P.M.B.), Division of Clinical Neuroscience, University of Nottingham, UK; Department of Neurology (L.C.), University of Debrecen Medical and Health Science Center, Hungary; Department of Neurology (W.H.), University of Heidelberg, Germany; Department of Neurology (P.J.K.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (D.L.), Roger Salengro Hospital, Lille, France; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Université Paris Descartes, France; Department of Neurology (R.L.S.), Miller School of Medicine, University of Miami, FL; and Department of Neurology and Stroke Center (P.A., L.S.), Bichat University Hospital, Paris, France. N.A.Hilkens-3@umcutrecht.nl. 2. From the Julius Center for Health Sciences and Primary Care (N.A.H., A.A., J.B.R., J.P.G.) and Department of Neurology and Neurosurgery (A.A., L.J.K.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (H.-C.D.), University Hospital Essen, Germany; Stroke Trials Unit (P.M.B.), Division of Clinical Neuroscience, University of Nottingham, UK; Department of Neurology (L.C.), University of Debrecen Medical and Health Science Center, Hungary; Department of Neurology (W.H.), University of Heidelberg, Germany; Department of Neurology (P.J.K.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (D.L.), Roger Salengro Hospital, Lille, France; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Université Paris Descartes, France; Department of Neurology (R.L.S.), Miller School of Medicine, University of Miami, FL; and Department of Neurology and Stroke Center (P.A., L.S.), Bichat University Hospital, Paris, France.
Abstract
OBJECTIVE: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. METHODS: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. RESULTS: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. CONCLUSIONS: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.
OBJECTIVE: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. METHODS: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. RESULTS: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. CONCLUSIONS: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.
Authors: Brian F Gage; Yan Yan; Paul E Milligan; Amy D Waterman; Robert Culverhouse; Michael W Rich; Martha J Radford Journal: Am Heart J Date: 2006-03 Impact factor: 4.749
Authors: Jeffrey S Berger; Deepak L Bhatt; P Gabriel Steg; Steven R Steinhubl; Gilles Montalescot; Mingyuan Shao; Werner Hacke; Keith A Fox; Peter B Berger; Eric J Topol; A Michael Lincoff Journal: Am Heart J Date: 2011-07 Impact factor: 4.749
Authors: Koon-Hou Mak; Deepak L Bhatt; Mingyuan Shao; Graeme J Hankey; J Donald Easton; Keith A A Fox; Eric J Topol Journal: Am Heart J Date: 2008-11-06 Impact factor: 4.749
Authors: Colin Baigent; Lisa Blackwell; Rory Collins; Jonathan Emberson; Jon Godwin; Richard Peto; Julie Buring; Charles Hennekens; Patricia Kearney; Tom Meade; Carlo Patrono; Maria Carla Roncaglioni; Alberto Zanchetti Journal: Lancet Date: 2009-05-30 Impact factor: 79.321
Authors: Charles E Leonard; Meijia Zhou; Colleen M Brensinger; Warren B Bilker; Samantha E Soprano; Thanh Phuong Pham Nguyen; Young Hee Nam; Jordana B Cohen; Sean Hennessy Journal: Clin Pharmacol Ther Date: 2019-07-04 Impact factor: 6.875
Authors: Nina A Hilkens; Ale Algra; Hans Christoph Diener; Philip M Bath; László Csiba; Werner Hacke; L Jaap Kappelle; Peter J Koudstaal; Didier Leys; Jean-Louis Mas; Ralph L Sacco; Jacoba P Greving Journal: Stroke Date: 2021-07-26 Impact factor: 7.914