TY - JOUR
T1 - Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage
AU - Al-Shahi Salman, Rustam
AU - Greenberg, Steven M
N1 - Funding Information:
We and others think that a definitive main phase RCT could resolve these remaining uncertainties and be integrated into physicians’ clinical routine (). Funding agencies in the Global Cardiovascular Research Funders Forum Multinational Clinical Trials Initiative ( https://www.bhf.org.uk/for-professionals/information-for-researchers/gcrff-multinational-clinical-trials-initiative ) and the Australian NHMRC Medical Research Future Fund have provided funding for ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage), to follow its external pilot phase (). This event-driven RCT aims to recruit 4148 CH survivors (2074 per group) over 4 years (starting in mid-2024) to detect 947 MACE primary outcome events over ≥1 year of follow-up if the MACE event rate is 11.1% per year in the comparator group, to detect an effect size of 0.81 from antiplatelet agents (aspirin or clopidogrel) with a 2-sided alpha of 0.05 and 90% power. RCTs after ASPRING may address specific questions about the timing of initiating antiplatelet agents (after ASPIRING explores effects in subgroups according to their time of randomization after ICH onset) and other antiplatelet agents () such as cilostazol (which was not superior to aspirin after ICH in the PICASSO [PreventIon of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage] RCT, but seems to have similar efficacy and a lower risk of hemorrhage compared with aspirin [mostly in Asian populations]). ,, ,,, , ,
Funding Information:
Dr Al-Shahi Salman was the chief investigator of RESTART (Restart or Stop Antithrombotics Randomised Trial; ISRCTN71907627) and SoSTART (Start or Stop Anticoagulants Randomized Trial; NCT03153150), funded by grants from the British Heart Foundation, Chest Heart & Stroke Scotland, and the UK Medical Research Council (all paid to The University of Edinburgh). Dr Al-Shahi Salman is a Co-Chief Investigator of the ASPIRING (Antiplatelet Secondary Prevention International Randomised Study After Intracerebral Haemorrhage) Pilot Phase (NCT04522102), funded by Australian National Health and Medical Research Council Program grants (APP1113352 and APP1149987) paid to the Universities of Western Australia and New South Wales and a grant from the Shanghai Shenkang Hospital Development Center paid to Huashan Hospital. Dr Al-Shahi Salman is the Chief Investigator of the ASPIRING main phase trial that has been funded by the British Heart Foundation, Hartstichting, Canadian Institutes of Health Research, and the Australian NHMRC. Dr Greenberg serves on the Clinical Trial Data Monitoring Committee for clinical trials in the Bayer Healthcare Pharmaceuticals Inc Oral Factor Xia Inhibitor Program and on the Steering Committee for the ASPIRE trial (Anticoagulation for Stroke Prevention and Recovery After ICH) trial (NCT03907046).
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/11/2
Y1 - 2023/11/2
N2 - 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.
AB - 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.
U2 - 10.1161/STROKEAHA.123.036886
DO - 10.1161/STROKEAHA.123.036886
M3 - Review article
C2 - 37916459
SN - 0039-2499
JO - Stroke
JF - Stroke
ER -