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Published on: June 4, 2021
Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage
Rustam Al-Shahi Salman1, Steven M Greenberg2
1The University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom (R.A.-S.S.).
Insights
Antiplatelet agents may be considered after intracerebral hemorrhage (ICH). The RESTART trial suggests they might not increase recurrent ICH risk, but larger studies like ASPIRING are needed for definitive answers.
Area of Science:
- Neurology and Cardiovascular Medicine
- Clinical Trial Research
- Pharmacological Interventions
Background:
- Intracerebral hemorrhage (ICH) survivors face high risks of major adverse cardiovascular events (MACE).
- Antiplatelet agents reduce MACE in non-ICH populations but may increase ICH risk.
- Previous guidance relied on risk-benefit estimations due to limited evidence post-ICH.
Purpose of the Study:
- To definitively determine the effects of antiplatelet agents on MACE and recurrent ICH in survivors.
- To evaluate antiplatelet therapy's efficacy and safety in specific subgroups of ICH survivors.
- To provide robust evidence for clinical decision-making regarding secondary prevention post-ICH.
Main Methods:
- The ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) trial aims to recruit 4148 ICH survivors.
- This large-scale randomized controlled trial will compare antiplatelet therapy against avoidance.
- Previous data from the RESTART trial (537 participants) and three smaller trials (174 participants) are insufficient for definitive conclusions.
Main Results:
- The RESTART trial (2019) suggested antiplatelet agents might not increase recurrent ICH risk compared to avoidance (4% vs. 9%, adjusted HR 0.51).
- However, the evidence level is classified as B, indicating further research is necessary.
- Existing trials are underpowered to reliably assess the impact on all MACE.
Conclusions:
- Current guidelines suggest antiplatelet agents may be considered after ICH, particularly if associated with antithrombotic use.
- The ASPIRING trial is designed to provide definitive evidence on the net clinical benefit of antiplatelet agents post-ICH.
- Results from ASPIRING will inform future clinical practice and guidelines for secondary prevention in ICH survivors.
Abstract:
This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral hemorrhage (ICH) complements earlier updates about blood pressure-lowering, lipid-lowering, and oral anticoagulation or left atrial appendage occlusion for atrial fibrillation after ICH. When used for secondary prevention in people without ICH, antiplatelet agents reduce the risk of major adverse cardiovascular event (rate ratio, 0.81 [95% CI, 0.75-0.87]) and might increase the risk of ICH (rate ratio, 1.67 [95% CI, 0.97-2.90]). Before 2019, guidance for clinical decisions about antiplatelet agent use after ICH has focused on estimating patients' predicted absolute risks and severities of ischemic and hemorrhagic major adverse cardiovascular event and applying the known effects of these drugs in people without ICH to estimate whether individual ICH survivors in clinical practice might be helped or harmed by antiplatelet agents. In 2019, the main results of the RESTART (Restart or Stop Antithrombotics Randomized Trial) randomized controlled trial including 537 survivors of ICH associated with antithrombotic drug use showed, counterintuitively, that antiplatelet agents might not increase the risk of recurrent ICH compared to antiplatelet agent avoidance over 2 years of follow-up (12/268 [4%] versus 23/268 [9%]; adjusted hazard ratio, 0.51 [95% CI, 0.25-1.03]; P=0.060). Guidelines in the United States, Canada, China, and the United Kingdom and Ireland have classified the level of evidence as B and indicated that antiplatelet agents may be considered/reasonable after ICH associated with antithrombotic agent use. Three subsequent clinical trials have recruited another 174 participants with ICH, but they will not be sufficient to determine the effects of antiplatelet therapy on all major adverse cardiovascular events reliably when pooled with RESTART. Therefore, ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) aims to recruit 4148 ICH survivors to determine the effects of antiplatelet agents after ICH definitively overall and in subgroups.
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