Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets

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...

Full description

Bibliographic Details
Main Authors: Hilkens, Nina A., Algra, Ale, Diener, Hans-Christoph, Reitsma, Johannes B., Bath, Philip M., Csiba, Laszlo, Hacke, Werner, Kappelle, L. Jaap, Koudstaal, Peter J., Leys, Didier, Mas, Jean-Louis, Sacco, Ralph L., Amarenco, Pierre, Sissani, Leila, Greving, Jacoba P.
Format: Article
Published: American Academy of Neurology 2017
Online Access:https://eprints.nottingham.ac.uk/49314/
_version_ 1848797970538954752
author Hilkens, Nina A.
Algra, Ale
Diener, Hans-Christoph
Reitsma, Johannes B.
Bath, Philip M.
Csiba, Laszlo
Hacke, Werner
Kappelle, L. Jaap
Koudstaal, Peter J.
Leys, Didier
Mas, Jean-Louis
Sacco, Ralph L.
Amarenco, Pierre
Sissani, Leila
Greving, Jacoba P.
author_facet Hilkens, Nina A.
Algra, Ale
Diener, Hans-Christoph
Reitsma, Johannes B.
Bath, Philip M.
Csiba, Laszlo
Hacke, Werner
Kappelle, L. Jaap
Koudstaal, Peter J.
Leys, Didier
Mas, Jean-Louis
Sacco, Ralph L.
Amarenco, Pierre
Sissani, Leila
Greving, Jacoba P.
author_sort Hilkens, Nina A.
building Nottingham Research Data Repository
collection Online Access
description 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.
first_indexed 2025-11-14T20:12:20Z
format Article
id nottingham-49314
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T20:12:20Z
publishDate 2017
publisher American Academy of Neurology
recordtype eprints
repository_type Digital Repository
spelling nottingham-493142020-05-04T19:02:57Z https://eprints.nottingham.ac.uk/49314/ Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets Hilkens, Nina A. Algra, Ale Diener, Hans-Christoph Reitsma, Johannes B. Bath, Philip M. Csiba, Laszlo Hacke, Werner Kappelle, L. Jaap Koudstaal, Peter J. Leys, Didier Mas, Jean-Louis Sacco, Ralph L. Amarenco, Pierre Sissani, Leila Greving, Jacoba P. 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. American Academy of Neurology 2017-08-29 Article PeerReviewed Hilkens, Nina A., Algra, Ale, Diener, Hans-Christoph, Reitsma, Johannes B., Bath, Philip M., Csiba, Laszlo, Hacke, Werner, Kappelle, L. Jaap, Koudstaal, Peter J., Leys, Didier, Mas, Jean-Louis, Sacco, Ralph L., Amarenco, Pierre, Sissani, Leila and Greving, Jacoba P. (2017) Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets. Neurology, 89 (9). pp. 936-943. ISSN 1526-632X http://n.neurology.org/content/89/9/936 doi:10.1212/WNL.0000000000004289 doi:10.1212/WNL.0000000000004289
spellingShingle Hilkens, Nina A.
Algra, Ale
Diener, Hans-Christoph
Reitsma, Johannes B.
Bath, Philip M.
Csiba, Laszlo
Hacke, Werner
Kappelle, L. Jaap
Koudstaal, Peter J.
Leys, Didier
Mas, Jean-Louis
Sacco, Ralph L.
Amarenco, Pierre
Sissani, Leila
Greving, Jacoba P.
Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title_full Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title_fullStr Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title_full_unstemmed Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title_short Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
title_sort predicting major bleeding in patients with noncardioembolic stroke on antiplatelets
url https://eprints.nottingham.ac.uk/49314/
https://eprints.nottingham.ac.uk/49314/
https://eprints.nottingham.ac.uk/49314/