Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke
Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients a...
| Main Authors: | , , , , , , |
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| Format: | Article |
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American Academy of Neurology
2018
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| Online Access: | https://eprints.nottingham.ac.uk/50290/ |
| _version_ | 1848798210839019520 |
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| author | Hilkens, Nina A. Algra, Ale Kappelle, L. Jaap Bath, Philip M. Csiba, László Rothwell, Peter M. Greving, Jacoba P. |
| author_facet | Hilkens, Nina A. Algra, Ale Kappelle, L. Jaap Bath, Philip M. Csiba, László Rothwell, Peter M. Greving, Jacoba P. |
| author_sort | Hilkens, Nina A. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy.
Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex.
Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy.
Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts. |
| first_indexed | 2025-11-14T20:16:09Z |
| format | Article |
| id | nottingham-50290 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:16:09Z |
| publishDate | 2018 |
| publisher | American Academy of Neurology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-502902020-05-04T19:28:28Z https://eprints.nottingham.ac.uk/50290/ Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke Hilkens, Nina A. Algra, Ale Kappelle, L. Jaap Bath, Philip M. Csiba, László Rothwell, Peter M. Greving, Jacoba P. Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts. American Academy of Neurology 2018-01-26 Article PeerReviewed Hilkens, Nina A., Algra, Ale, Kappelle, L. Jaap, Bath, Philip M., Csiba, László, Rothwell, Peter M. and Greving, Jacoba P. (2018) Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology, 90 (8). e683-e689. ISSN 1526-632X http://n.neurology.org/content/90/8/e683 doi:10.1212/WNL.0000000000004997 doi:10.1212/WNL.0000000000004997 |
| spellingShingle | Hilkens, Nina A. Algra, Ale Kappelle, L. Jaap Bath, Philip M. Csiba, László Rothwell, Peter M. Greving, Jacoba P. Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title | Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title_full | Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title_fullStr | Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title_full_unstemmed | Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title_short | Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke |
| title_sort | early time course of major bleeding on antiplatelet therapy after tia or ischemic stroke |
| url | https://eprints.nottingham.ac.uk/50290/ https://eprints.nottingham.ac.uk/50290/ https://eprints.nottingham.ac.uk/50290/ |