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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.

Authors

Nina A. Hilkens

Ale Algra

L. Jaap Kappelle

Philip M. Bath

László Csiba

Peter M. Rothwell

Jacoba P. Greving



Abstract

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.

Citation

Hilkens, N. A., Algra, A., Kappelle, L. J., Bath, P. M., Csiba, L., Rothwell, P. M., & Greving, J. P. (2018). Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology, 90(8), https://doi.org/10.1212/WNL.0000000000004997

Journal Article Type Article
Acceptance Date Nov 14, 2017
Publication Date Jan 26, 2018
Deposit Date Mar 7, 2018
Publicly Available Date Mar 7, 2018
Journal Neurology
Print ISSN 0028-3878
Electronic ISSN 1526-632X
Publisher American Academy of Neurology
Peer Reviewed Peer Reviewed
Volume 90
Issue 8
Article Number e683-e689
DOI https://doi.org/10.1212/WNL.0000000000004997
Public URL http://eprints.nottingham.ac.uk/id/eprint/50290
Publisher URL http://n.neurology.org/content/90/8/e683
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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