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Randomized Controlled Trial
. 2021 Oct 1;78(10):1179-1186.
doi: 10.1001/jamaneurol.2021.2956.

Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage: Extended Follow-up of the RESTART Randomized Clinical Trial

Rustam Al-Shahi Salman  1   2 , Martin S Dennis  1 , Peter A G Sandercock  1 , Cathie L M Sudlow  1   2   3 , Joanna M Wardlaw  1   4   5 , William N Whiteley  1 , Gordon D Murray  2 , Jacqueline Stephen  2 , Aryelly Rodriguez  2 , Steff Lewis  2 , David J Werring  6 , Phil M White  7   8 ; RESTART Collaboration
Collaborators, Affiliations
Randomized Controlled Trial

Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage: Extended Follow-up of the RESTART Randomized Clinical Trial

Rustam Al-Shahi Salman et al. JAMA Neurol. .

Abstract

Importance: The Restart or Stop Antithrombotics Randomized Trial (RESTART) found that antiplatelet therapy appeared to be safe up to 5 years after intracerebral hemorrhage (ICH) that had occurred during antithrombotic (antiplatelet or anticoagulant) therapy.

Objectives: To monitor adherence, increase duration of follow-up, and improve precision of estimates of the effects of antiplatelet therapy on recurrent ICH and major vascular events.

Design, setting and participants: From May 22, 2013, through May 31, 2018, this prospective, open, blinded end point, parallel-group randomized clinical trial studied 537 participants at 122 hospitals in the UK. Participants were individuals 18 years or older who had taken antithrombotic therapy for the prevention of occlusive vascular disease when they developed ICH, discontinued antithrombotic therapy, and survived for 24 hours. After initial follow-up ended on November 30, 2018, annual follow-up was extended until November 30, 2020, for a median of 3.0 years (interquartile range [IQR], 2.0-5.0 years) for the trial cohort.

Interventions: Computerized randomization that incorporated minimization allocated participants (1:1) to start or avoid antiplatelet therapy.

Main outcomes and measures: Participants were followed up for the primary outcome (recurrent symptomatic ICH) and secondary outcomes (all major vascular events) for up to 7 years. Data from all randomized participants were analyzed using Cox proportional hazards regression, adjusted for minimization covariates.

Results: A total of 537 patients (median age, 76.0 years; IQR, 69.0-82.0 years; 360 [67.0%] male; median time after ICH onset, 76.0 days; IQR, 29.0-146.0 days) were randomly allocated to start (n = 268) or avoid (n = 269 [1 withdrew]) antiplatelet therapy. The primary outcome of recurrent ICH affected 22 of 268 participants (8.2%) allocated to antiplatelet therapy compared with 25 of 268 participants (9.3%) allocated to avoid antiplatelet therapy (adjusted hazard ratio, 0.87; 95% CI, 0.49-1.55; P = .64). A major vascular event affected 72 participants (26.8%) allocated to antiplatelet therapy compared with 87 participants (32.5%) allocated to avoid antiplatelet therapy (hazard ratio, 0.79; 95% CI, 0.58-1.08; P = .14).

Conclusions and relevance: Among patients with ICH who had previously taken antithrombotic therapy, this study found no statistically significant effect of antiplatelet therapy on recurrent ICH or all major vascular events. These findings provide physicians with some reassurance about the use of antiplatelet therapy after ICH if indicated for secondary prevention of major vascular events.

Trial registration: isrctn.org Identifier: ISRCTN71907627.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dennis reported receiving grants from the British Heart Foundation during the conduct of the study. Dr Sudlow reported receiving grants from the British Heart Foundation during the conduct of the study. Dr Wardlaw reported receiving grants from the Scottish Funding Council during the conduct of the study and grants from Fondation Leducq, British Heart Foundation, EU H2020, UK Stroke Association, Medical Research Council, and Alzheimer’s Society outside the submitted work. Dr Murray reported receiving grants from the British Heart Foundation during the conduct of the study. Dr Werring reported receiving personal fees from Bayer, Alexion/Portola, Alnylam, and NovoNordisk outside the submitted work. Dr White reported receiving grants from Stryker, Penumbra, Medtronic, and Microvention and personal fees from Microvention outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram
Reprinted with permission from RESTART Collaboration.
Figure 2.
Figure 2.. Risk of the First Occurrence of Recurrent Symptomatic Intracerebral Hemorrhage
Numbers at risk refer to survivors undergoing follow-up at the start of each year according to treatment allocation. Plot was censored at 5 years. Cumulative events indicate the participants in follow-up with a first event.
Figure 3.
Figure 3.. Risk of the First Occurrence of a Major Vascular Event
Numbers at risk refer to survivors under follow-up at the start of each year according to treatment allocation. Plot was censored at 5 years. Cumulative events indicate the participants in follow-up with a first event.
See this image and copyright information in PMC

Comment in

References

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