White matter lesion effect modification of aspirin and unfractionated heparin during endovascular stroke treatment.
Authors
Affiliations (13)
Affiliations (13)
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands. [email protected].
- Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, The Netherlands. [email protected].
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. [email protected].
- Amsterdam Neuroscience, Amsterdam, The Netherlands. [email protected].
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
- Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, The Netherlands.
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
- Amsterdam Neuroscience, Amsterdam, The Netherlands.
- Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands.
- Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA.
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
- Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
- Department of Brain Sciences, Imperial College London, London, UK.
Abstract
Periprocedural aspirin or unfractionated heparin during endovascular treatment in acute ischemic stroke increases symptomatic intracranial hemorrhage (sICH) risk without improving functional outcome. White matter lesions (WMLs) are associated with higher sICH risk and poor functional outcome following stroke. We aimed to assess whether WML volume modifies the effect of aspirin or heparin. In this post-hoc analysis of the MR CLEAN-MED trial, WML volume was automatically determined using deep learning-based segmentation on baseline non-contrast CT scans. Outcomes included good functional outcome (modified Rankin Scale 0-2 at 90 days), any ICH, asymptomatic ICH (aICH), and sICH. Patients received either aspirin or not, and either heparin or not. Multivariable logistic regression evaluated treatment effect and effect modification. Of 628 patients, 614 with baseline CT were included. Median WML volume was 0.59 mL without significant differences between treatment arms. WML volume significantly modified the effect of aspirin on sICH (p = 0.01), but not on functional outcome (p = 0.95), any ICH (p = 0.52), or aICH (p = 0.30). Aspirin was associated with increased sICH risk, which decreased with increasing WML volume (aOR 0.96 [95% CI: 0.93-0.99] per 1 mL). For patients with large WML volumes, aspirin showed no significant effect on sICH risk. The effect of heparin on functional outcome, any ICH, aICH, and sICH was not modified by WML volume (p = 0.53, p = 0.26, p = 0.08, p = 0.63, respectively). WML volume significantly modified the effect of aspirin on sICH risk, with aspirin-associated risk decreasing as WML volume increased. WML volume did not modify the effect of aspirin or heparin on other outcomes. WML volume on non-contrast CT modifies the effect of aspirin during endovascular thrombectomy on sICH risk, yet no WML-based patient subgroup showed save benefits from periprocedural aspirin or heparin treatment. Periprocedural aspirin and unfractionated heparin during endovascular treatment cause a higher hemorrhage risk. WML volume is associated with worse functional outcome and WML volume significantly modifies the effect of aspirin on symptomatic hemorrhage risk, with aspirin-associated risk decreasing with increasing WML volume. No WML-volume-based patient subgroup was identified where aspirin or heparin treatment demonstrated safe clinical benefit.