Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 20:2:40.
doi: 10.1186/s42466-020-00087-9. eCollection 2020.

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial

Benedikt M Frey  1 , Florent Boutitie  2   3   4 , Bastian Cheng  1 , Tae-Hee Cho  5 , Martin Ebinger  6   7 , Matthias Endres  6   8 , Jochen B Fiebach  6 , Jens Fiehler  9 , Ian Ford  10 , Ivana Galinovic  6 , Alina Königsberg  1 , Josep Puig  11 , Pascal Roy  2   3   4 , Anke Wouters  12   13   14 , Tim Magnus  1 , Vincent Thijs  15   16 , Robin Lemmens  12   13   14 , Keith W Muir  17 , Norbert Nighoghossian  5 , Salvador Pedraza  11 , Claus Z Simonsen  18 , Christian Gerloff  1 , Götz Thomalla  1 ; WAKE-UP investigators
Collaborators, Affiliations

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial

Benedikt M Frey et al. Neurol Res Pract. .

Abstract

Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).

Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.

Keywords: Alteplase; Antiplatelet; Aspirin; Clopidogrel; Hemorrhagic transformation; Ischemic stroke; Recombinant human tissue plasminogen activator; Rt-PA; Thrombolysis; WAKE UP.

PubMed Disclaimer

Conflict of interest statement

Competing interestsEB reports grants from the German Parkinson Society and ACTELION Pharmaceuticals Deutschland GmbH, outside the submitted work. FB reports grants from University Medical Center Hamburg-Eppendorf during the conduct of the study. ME reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Amgen, GlaxoSmithKlineGSK, Sanofi, Covidien, Ever, Novartis, all outside the submitted work. JBF reports personal fees from Bioclinica, Artemida, Cerevast, and Nicolab outside the submitted work. TM reports grants from DFG, BMBF, the Schilling Foundation, Merck-Serono and Grifols, outside the submitted work. VT reports personal fees and non-financial support from Boehringer Ingelheim, Pfizer/BMS, Bayer, Sygnis, Amgen and Allergan outside the submitted work. KWM reports personal fees and non-financial support from Boehringer Ingelheim outside the submitted work. CZS reports grants from Novo Nordisk Foundation and personal fees from Bayer outside the submitted work. CG reports personal. fees from AMGEN, Bayer Vital, BMS, Boehringer Ingelheim, Sanofi Aventis, Abbott, and Prediction Biosciences outside the submitted work. GT reports personal fees from Acandis, Boehringer Ingelheim, BMS/Pfizer, Stryker, Portola, Daiichi Sankyo, grants and personal fees from Bayer, grants from Corona Foundation, German Innovation Fonds and Else Kroener Fresenius Foundation outside the submitted work. All remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effect of alteplase on hemorrhagic transformation. Forest plots demonstrate a significant higher chance of developing any sign of hemorrhagic transformation during follow-up for patients treated with alteplase in both patients with prior APT and without. There was no significant interaction in the corresponding unconditional logistic regression model
Fig. 2
Fig. 2
Effect of alteplase on favorable outcome. Forest plots demonstrate a higher chance of a favorable functional outcome for patients treated with alteplase in both patients with prior APT and without. There was no significant interaction in the corresponding unconditional logistic regression model
Fig. 3
Fig. 3
Distribution of modified Rankin scale scores at 90 days after stroke. Distributions of scores on the modified Rankin scale show a favoring of the alteplase group over the placebo group. Modified Rankin scale scores range from 0 to 6 (0, no symptoms; 1, no clinically significant disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; 5, severe disability; 6, death). Numbers indicate rounded proportions. There was no significant interaction in the corresponding unconditional logistic regression model
See this image and copyright information in PMC

References

    1. Diedler J, Ahmed N, Sykora M, Uyttenboogaart M, Overgaard K, Luijckx GJ, et al. Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke. 2010;41(2):288–294. doi: 10.1161/STROKEAHA.109.559724. - DOI - PubMed
    1. Dowlatshahi D, Hakim A, Fang J, Sharma M, Investigators of the Registry of the Canadian Stroke Network Pre admission antithrombotics are associated with improved outcomes following ischaemic stroke: a cohort from the registry of the Canadian stroke network. International Journal of Stroke : Official Journal of the International Stroke Society. 2009;4(5):328–334. doi: 10.1111/j.1747-4949.2009.00331.x. - DOI - PubMed
    1. Goldstein LB, Samsa GP, Matchar DB, Horner RD. Charlson index comorbidity adjustment for ischemic stroke outcome studies. Stroke. 2004;35(8):1941–1945. doi: 10.1161/01.STR.0000135225.80898.1c. - DOI - PubMed
    1. Luo S, Zhuang M, Zeng W, Tao J. Intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy: a systematic review and meta-analysis of 19 studies. Journal of the American Heart Association. 2016;5(5):e003242. doi: 10.1161/JAHA.116.003242. - DOI - PMC - PubMed
    1. Malhotra K, Katsanos AH, Goyal N, Ahmed N, Strbian D, Palaiodimou L, et al. Safety and efficacy of dual antiplatelet pretreatment in patients with ischemic stroke treated with IV thrombolysis: a systematic review and meta-analysis. Neurology. 2020;94(7):e657–e666. doi: 10.1212/WNL.0000000000008961. - DOI - PubMed

LinkOut - more resources