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Randomized Controlled Trial
. 2024 Sep 1;81(9):958-965.
doi: 10.1001/jamaneurol.2024.2404.

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial

Babak B Navi  1   2 , Cenai Zhang  1 , Benjamin Miller  3 , Mary Cushman  4 , Scott E Kasner  5 , Mitchell S V Elkind  6   7 , David L Tirschwell  8 , W T Longstreth Jr  8   9 , Richard A Kronmal  10 , Morin Beyeler  1   11 , Jordan Elm  12 , Richard M Zweifler  13 , Joseph Tarsia  13 , Carlo W Cereda  14 , Giovanni Bianco  14 , Gianluca Costamagna  15   16 , Patrik Michel  17 , Joseph P Broderick  18 , David J Gladstone  19 , Hooman Kamel  1   20 , Christopher Streib  3
Affiliations
Randomized Controlled Trial

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial

Babak B Navi et al. JAMA Neurol. .

Abstract

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke.

Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke.

Design, setting, and participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024.

Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined.

Main outcomes and measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage.

Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]).

Conclusions and relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin.

Trial registration: ClinicalTrials.gov Identifier: NCT03192215.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Navi reported receiving grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study; and receiving personal fees from MindRhythm Inc outside the submitted work. Dr Kasner reported receiving grants from Diamedica, Bristol Myers Squibb, Bayer, Daiichi Sankyo, Genentech, and WL Gore, personal fees from AstraZeneca and NovoNordisk, and royalties from UpToDate outside the submitted work. Dr Elkind reported receiving salary from the American Heart Association and royalties from UpToDate outside the submitted work. Dr Tirschwell reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Longstreth reported receiving grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Beyeler reported receiving grants from the University of Bern outside the submitted work. Dr Elm reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Cereda reported receiving personal fees from iSchemaView outside the submitted work. Dr Michel reported receiving grants from the Swiss National Science Foundation, Swiss Heart Foundation, and Faculty of Biology and Medicine of the University of Lausanne outside the submitted work. Dr Broderick reported receiving study medication from Novo Nordisk, grants from the National Institute of Neurological Disorders and Stroke and Roche-Genentech, and consultant fees from Basking Biosciences, Brainsgate, and Kroger Prescription Plans Inc outside the submitted work. Dr Gladstone reported receiving grants from Bayer, the Heart and Stroke Foundation of Canada, and the Department of Medicine at Sunnybrook Health Sciences Centre and University of Toronto outside the submitted work. Dr Kamel reported serving on clinical trial steering or executive committees for Medtronic, Janssen, and Boston Scientific; serving on consulting or end point adjudication committees for AbbVie, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and having household ownership interests in TETMedical, Spectrum Plastics Group, and Ascential Technologies outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Rates of Major Ischemic or Major Hemorrhagic Events in Participants With Cancer Randomized to Apixaban vs Aspirin
Kaplan-Meier curves estimate the cumulative incidence functions of major ischemic or major hemorrhagic events among participants with history of cancer on enrollment in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial. The shaded areas represent the 95% CIs for the estimated rates. Hashmarks represent participant censoring for death, withdrawal, or loss to follow-up.
Figure 2.
Figure 2.. Cumulative Rates of Recurrent Stroke in Participants With Cancer Randomized to Apixaban vs Aspirin
Kaplan-Meier curves estimate the cumulative incidence functions of recurrent ischemic or hemorrhagic stroke among participants with history of cancer on enrollment in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial. The shaded areas represent the 95% CIs for the estimated rates. Hashmarks represent participant censoring for death, withdrawal, or loss to follow-up.
See this image and copyright information in PMC

References

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