Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke

Abstract

Background and Purpose-Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone. Methods-In a case-crossover study, 31 patients with previous atherothrombotic or lacunar stroke who were treated with aspirin (100 to 300 mg/d) received clopidogrel (75 mg/d) and both aspirin and clopidogrel for 4 weeks. Platelet function in whole blood was studied after each treatment period and in healthy control subjects to assess activation-dependent antigens CD62p and CD63 by flow cytometry and collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times with the platelet function analyzer PFA-100, which investigates platelet-related function under shear stress. Results-CD62p expression and CD63 expression were not different under the 3 treatment regimens. CD63 but not CD62p expression was lower in control subjects than in stroke patients regardless of the antiplatelet treatment (PϽ0.05). CEPI-CT was prolonged under aspirin and aspirin plus clopidogrel compared with clopidogrel monotherapy (PϽ0.0001). CADP-CT was longer under combination therapy than under aspirin (Pϭ0.0009) or clopidogrel (Pϭ0.0074) or in control subjects (Pϭ0.0010), mainly because of strong prolongation in a patient subgroup (28%). Conclusions-CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage. The predictive value of platelet activation parameters requires investigation in prospective studies. Key Words: inflammation Ⅲ platelet aggregation inhibitors Ⅲ platelets Ⅲ secondary prevention A ntiplatelet drugs are the treatment of choice for secondary prevention after cerebral ischemia of noncardioembolic origin. However, the efficacy of presently available drugs is limited. Compared with placebo, aspirin reduced the relative risk of vascular events by 13% according to two meta-analyses 1,2 and stroke risk by 18% in the European Stroke Prevention Study 2. 3 Under clopidogrel, the relative risk of a compound outcome cluster of stroke, myocardial infarction, and vascular death was marginally, although significantly, lower than under aspirin (Ϫ8.4%), whereas the risk reduction for stroke alone was not significant. 4 Aspirin inhibits platelet aggregation by inhibition of cyclooxygenase, whereas clopidogrel reduces platelet activation via ADP receptor-dependent pathways. On the basis of these different modes of action, it is an attractive concept that the combination of both drugs may have additive effects on platelet See Editorial Comment, page 854 inhibition. The combination of aspirin and clopidogrel or ticlopidine was shown to be a successful treatment strategy after coronary stenting and in unstable angi...

Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

“…1) [10,12,13,14,15,22,23,24]. A total of 18 studies were excluded: four were excluded because they were not RCTs [25,26,27,28], three were excluded because the comparator was not aspirin or clopidogrel alone [29,30,31], seven were excluded for lack of specific data [9,32,33,34,35,36,37], two were excluded since the trials were ongoing [38,39], and two were excluded due to redundancy [40,41]: the original study reported both primary and secondary prevention, and the subsequent report [14] focused on results in patients with previous TIA or ischemic stroke. The baseline characteristics of included studies are summarized in table 1.…”

Association of Recurrent Cerebral Infarction With Adenosine Diphosphate– and Collagen-Induced Platelet Aggregation in Patients Treated With Ticlopidine and/or Aspirin

“…Along with standard platelet aggregation, PFA-100 has been used to monitor antiplatelet therapy in patients with ischemic stroke 17,[23][24][25][26] The method uses a combination of 2 agonists, collagen/epinephrine or collagen/ADP, to stimulate platelet aggregation. Measuring PFA-100 closure time has potential for monitoring the inhibitory effects of various antiplatelet drugs.…”

“…However, except for the study of Grundmann et al, 17 most previous studies were not able to show that PFA-100 can predict the recurrence of ischemic stroke, suggesting that the platelet aggregation approach may have limitations in monitoring antiplatelet therapy with various antiplatelet drugs. In other attempts to evaluate platelet activation, expression levels of platelet receptors, including P-selectin (CD62p), 23 lysosome-associated membrane protein (CD63), 23 PECAM-1 (CD31), 26 GP IIb/IIIa (CD41), 26 Figure 2. Recurrence rates of quartiles according to platelet aggregation in the aspirin group.…”

Clopidogrel-Induced Platelet Inhibition Cannot Be Detected by the Platelet Function Analyzer-100 System in Stroke Patients

“…6 In contrast, another study found that, the PFA-100 system was sensitive to clopidogrel effects in a subset of stroke patients. 11 Another recent study reported a considerable time lag before relevant clopidogrelinduced antiplatelet effects could be measured in stroke patients. 12 With respect to a possible delay in the detection of antiaggregatory effects, we further analyzed our data and stratified the study population into 2 groups; stroke patients treated with clopidogrel for Ͻ3 weeks and Ͼ3 weeks (short-term vs long-term therapy).…”