Argatroban versus aspirin plus clopidogrel in the treatment of acute ischemic stroke: A pilot, randomised, open-label study / 解放军医学杂志

ABSTRACT

Objective To evaluate the efficacy and safety of argatroban versus aspirin plus clopidogrel in the treatment of acute ischemic stroke. Methods Seventy five patients with acute ischemic stroke within 48h of symptom onset were randomly divided into two groups argatroban group (argatroban was used for 7 days according to the instructions, followed by aspirin 100mg per day plus clopidogrel 75mg per day until discharge, n=35), and combination antiplatelet group (300mg of clopidogrel for the first day, then 75mg daily plus aspirin 100mg daily until discharge, n=40). Oxfordshire Community Stroke Project (OCSP) classification was assessed in patients before treatment. National Institutes of Health Stroke Scale (NIHSS) was used for rating neurological deficit score of patients, and Barthel index for rating activities of daily life (ADL), and modified Rankin scale for handicap score. NIHSS was assessed one week after enrollment, while ADL and mRS assessment were recorded 3 months after onset. Brain imaging, liver and kidney function, blood routine tests and blood coagulation capacity of the patients were measured before and one week after enrollment to observe changes in hemorrhage and biochemical indicators. Drugs-related adverse events were recorded during treatment. All patients received TOAST analysis before leaving hospital. Results 1. In both groups, NIHSS was reduced after oneweek treatment, compared with that before treatment, while ADL was improved at three-month follow-up, compared with those at admission. The results showed statistically significant difference (P0.05) was found between two groups. The transient ischemic attacks (TIA) disappeared in both groups. Brain imaging showed that in three patients the lesion advanced to infarction in argatroban group (total 6 patients), and two patients in the combined antiplatelet group (total 5 patients) suffered from the same change. 2. The brain imaging and measuring of relevant laboratory indicators of patients in both groups were performed again after one-week treatment. There was no bleeding events (including intracranial hemorrhage and hemorrhage in other organs) or impairment of hepatorenal function (P>0.05). 3. In both groups, OCSP classifications of patients were mainly divided into the partial anterior circulation infarction (PACI), lacunar infarction (LACI) and posterior circulation infarction (POCI), while TOAST etiological analyses of patients were mainly large-artery atherosclerosis (LAA) and small artery occlusion (SAO). In both groups, the neurological defects were improved after treatment, and there was no significant bleeding events during treatment period. There was no significant difference of NIHSS one week after enrollment between PACI subgroups (P>0.05), while better neurological improvement was showed in the POCI subgroup of argatroban group. Conclusions Argatroban anticoagulant and combination antiplatelet therapy with aspirin plus clopidogrel can effectively improve neurological deficit of patients, reduce recurrence rate and deterioration of the illness in acute phase, and improve patients' daily activities (ADL). Argatroban therapy showed better neurological function improvement in the posterior circulation infarction patients. As a new anticoagulant drug, argatroban is safe in the treatment of acute ischemic stroke. For the patients who have infarction involving the posterior circulation, argatroban, as a more aggressive treatment, should be recommended. (The trial registered number ChiCTR TRC-13003384)