Efficacy and Safety of Intravenous Thrombolysis in Acute Ischemic Stroke Due to Small Vessel Occlusion : a Multicenter Retrospective Observational Study

Abstract

Backgrounds: Small vessel occlusion (SVO) accounts for 15-20% of acute ischemic stroke (AIS). Given the mechanism of vessel occlusion, sharing pathophysiology with intracerebral hemorrhage (ICH), and minor symptom presentation, the efficacy and safety of intravenous tissue plasminogen activator (IV-TPA) in patients with AIS due to SVO remain unclear, particularly in Asian patients who are at a higher ICH risk than other populations.

Methods: Using a multicenter stroke registry of 15 centers in South Korea, we identified patients with AIS due to SVO admitted within 24 h from onset. The other inclusion criteria were prestroke mRS score 0-1, initial NIHSS <11, and 3-month mRS score available. The IV-TPA group included patients who were treated with IV-TPA within 4.5 h from onset in the participating centers. The control group included patients who did not receive IV-TPA. The primary and secondary efficacy outcomes were 3-month mRS 0-1 and mRS distribution. Safety outcomes were symptomatic ICH and 3-month mortality. Multivariable analysis was used to adjust baseline imbalances.

Results: Between FEB 1, 2011 and JAN 31, 2016, we identified 202 patients in the IV-TPA group and 2381 patients in the control group. The IV-TPA group versus the control group had higher median (IQR) NIHSS score (5 [4-6] vs 2 [1-4]) and shorter onset-to-arrival time (1 [1-2] vs 10 [4-16], h). In addition, the TPA group compared to the control group had more prestroke mRS 0, less prior stroke, more males, higher initial SBP, less prestroke antiplatelet, less prestroke statin, and less aspirin/clopidogrel dual therapy after admission. At 3 months, 116 (57.4%) in the IV-TPA group and 1589 (66.7%) in the control group had mRS 0-1. No patients in the IV-TPA group and 19 (0.8%) in the control group died. On multivariable analyses adjusting for covariates, adjusted OR (95% CI) with IV-TPA was 1.55 (1.06-2.27) (P=0.022) for 3-month mRS 0-1 outcome, 1.38 (1.02-1.86) (P=0.039) for 3-month mRS favorable shift, and 0.15 (0.01-2.18) (P=0.166) for 3-month mortality. Three (1.5%) in the IV-TPA group and one (0.04%) in the control group had symptomatic ICH.

Conclusion: This observational study suggests that IV-TPA improves outcome in patients with AIS due to SVO with an acceptable risk of symptomatic ICH.