The Safety of Clopidogrel Loading Therapy in Acute Ischemic Stroke Patients with Chronic Hemorrhage on Gradient Echo MRI

Objective: To determine if an acute loading dose of clopidogrel is safe in acute ischemic stroke (AIS) patients with chronic intracerebral hemorrhage (ICH). Background: Clopidogrel loading is a promising therapy for AIS patients not eligible for tissue plasminogen activator (tPA) who are at risk for progressive stroke. Previous ICH is a risk factor for developing a new ICH. However, the acute risk of these events in this population after loading with clopidogrel has not been studied. Methods: We examined 1,011 AIS patients presenting to our center from 06/07/07-07/31/13. Only those loaded with at least 300mg of clopidogrel (with or without aspirin) within 6 hours of admission were analyzed. We compared new onset hemorrhagic complications in patients with and without chronic ICH, defined as areas of parenchymal hypodensity on gradient recall echo (GRE) sequencing on MRI. Repeat CT or MRI during admission was evaluated by a vascular neurologist for evidence of new ICH, hemorrhagic infarct using ECASS II criteria, or new ischemic infarct. Results: Of 365 AIS patients loaded with clopidogrel, 67 had chronic ICH on GRE. Patients with chronic ICH were more likely to be African American (80.0% vs. 65.9%, p=0.028) and male (69.2% vs. 50.9%, p=0.008). These patients were more likely to have existing comorbidities: history of stroke (67.7% vs 37.5%, p<0.001), hypertension (90.8% vs 78.2%, p=0.021), and hyperlipidemia (56.9% vs 42.5%, p=0.036). After logistic regression analysis adjusting for significant covariates, chronic ICH patients did not have significant differences in any new hemorrhagic changes (p=0.709), new infarct (p=0.429), neuroworsening (defined as an increase in NIHSS score by 2 points within 24 hours, p=0.297), poor functional outcome (defined as modifed Rankin Scale > 2 on discharge, p=0.889), or unfavorable discharge disposition (defined as disposition other than home or inpatient rehabilitation, p=0.166). Conclusion: The presence of chronic ICH on GRE did not increase the risk of new ICH, hemorrhagic infarct, ischemic event, or neurologic deterioration after administration of an acute loading dose of clopidogrel for AIS.