LOAD: A Pilot Study of the Safety of Loading of Aspirin and Clopidogrel in Acute Ischemic Stroke and Transient Ischemic Attack

Abstract

Background: Most patients with ischemic stroke present to the emergency department beyond the approved 3-hour time window for thrombolytic or other revascularization therapies. Clopidogrel and aspirin loading is commonly used to prevent deterioration in other acute vascular occlusive events. This pilot study examined the safety of antiplatelet loading in acute ischemic stroke and transient ischemic attack.

Pilot Study of the Safety of Starting Administration of Low-Dose Aspirin and Cilostazol in Acute Ischemic Stroke

“…Examination of 40 acute ischemic stroke patients with a mean initial NIHSS score of 6 found the incidence of progressive stroke was 0% with the combination of aspirin and clopidogrel, if neurological deterioration was defined as an increase of 2 points or more on NIHSS, but symptomatic intracranial hemorrhage occurred at 43 hours posttreatment in one patient. 17) The present protocol of low-dose aspirin and cilostazol for acute ischemic stroke had a tolerable …”

“…2,4,8,9,13,14,17,20,22,27,30) Patients with progressive stroke have worse neurological scores on the initial NIHSS, and the greatest likelihood of predicting progression occurs with stratification by initial NIHSS scores of 7 or less and more than 7. 9,30) Therefore, the low incidence of progressive stroke in this study may be tied to the tendency to enroll mild cases.…”

“…1,5,[19][20][21]25) Several clinical trials have assessed the safety of acute antiplatelet therapy in ischemic stroke, but no standard treatment has been established for preventing stroke progression. 12,16,17,28) Cilostazol, an antiplatelet agent that increases cyclic adenosine monophosphate levels in platelets via selective inhibition of phosphodiesterase 3 and reduces platelet aggregation about 3 hours after single administration, 31) is as effective as aspirin in the secondary prevention of ischemic stroke. 10,23) In addition, cilostazol does not increase the frequency of intracranial hemorrhage compared with placebo, and K. Fujita et al…”

Potential new uses of non–vitamin K antagonist oral anticoagulants to treat and prevent stroke

“…45 The combination of aspirin and clopidogrel in patients with mild deficits was associated with a lower risk of neurologic deterioration compared with matched controls (OR 17.2, p 5 0.002). 46 In those patients, mechanisms such as a substenotic ulcerated plaque in the main vessel may be the cause. Indirect evidence for a more aggressive antithrombotic approach among patients with small vessel disease also comes from the original National Institute of Neurological Disorders and Stroke trial of IV tissue plasminogen activator in acute ischemic stroke, which demonstrated an even greater benefit for tissue plasminogen activator treatment among patients with small vessel stroke (25% absolute risk reduction of a poor outcome on the Barthel Index) than among patients with other stroke subtypes.…”

Antiplatelet Loading Improves Behavioral Outcome in a Rabbit Model of Stroke

“…1 Human studies have shown improved stroke outcome with acute antiplatelet loading, with no significant risk of hemorrhage. [2][3][4] The purpose of this proofof-concept study was to evaluate dose-related efficacy of acute antiplatelet loading on stroke outcome by comparing the following: (1) standard treatment of aspirin (ASA; 5 mg/kg), (2) usual dose dual antiplatelet loading (UD; ASA 10 mg/kg+10 mg/kg clopidogrel), and (3) high-dose dual antiplatelet loading (HD; ASA 10 mg/kg+30 mg/kg clopidogrel). Coprimary end points were (1) platelet inhibition and (2) behavioral outcome as measured by the P 50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group) 24 hours after stroke in the rabbit small clot embolic stroke model.…”