Pre-Admission Antiplatelet Therapy in Cryptogenic Stroke: A Double-Edged Sword

<b>Background</b>: Cryptogenic stroke, a challenging subtype of acute ischemic stroke (AIS), is characterized by the absence of an identifiable etiology despite thorough diagnostic assessment. The role of pre-admission antiplatelet therapy (APT) in this population remains poorly understood, as current guidelines are primarily based on evidence from other stroke subtypes. Therefore, this study investigates the impact of pre-admission APT on functional outcomes in patients with cryptogenic stroke. <b>Methods:</b> A total of 224 patients with cryptogenic stroke admitted to the University of Pécs between February 2023 and September 2024 were retrospectively analyzed. Propensity score matching (PSM) with sensitivity analysis was employed to balance baseline characteristics, resulting in a matched cohort of 122 patients. Logistic regression and mediation analysis were used to evaluate the association between pre-admission APT and favorable outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2. <b>Results:</b> A favorable outcome was achieved by 39.3% of patients with pre-admission APT (<i>n</i> = 61), compared to 61.7% of those not receiving pre-admission APT (<i>n</i> = 162) (odds ratio [OR] = 0.40, 95% confidence interval [CI]: 0.22-0.74, <i>p</i> = 0.004). After PSM and adjusting for confounders, including pre-morbidity mRS (pre-mRS) (OR = 0.17, CI: 0.06-0.49, <i>p</i> < 0.001), National Institutes of Health Stroke Scale (NIHSS) at 72 h post-stroke (OR = 0.67, CI: 0.50-0.88, <i>p</i> = 0.004), and smoking status (OR = 0.14, CI: 0.02-0.78, <i>p</i> = 0.025), pre-admission APT remained associated with poorer functional outcomes (adjusted OR [aOR] = 0.21, 95% CI: 0.06-0.76, <i>p</i> = 0.018). <b>Conclusions:</b> Pre-admission APT is independently associated with poorer functional outcomes in cryptogenic stroke patients. These findings challenge traditional assumptions regarding APT's protective role and highlight the need for prospective studies to refine its use in cryptogenic stroke management.