White matter lesion effect modification of aspirin and unfractionated heparin during endovascular stroke treatment

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CRITICAL RELEVANCE STATEMENT: 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. KEY POINTS: 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.