Aspirin-clopidogrel Therapy Research Articles

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear. A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment(modified Rankin scale ≥ 3) during follow-up. Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01). Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

Heart groups release partial update to atrial fibrillation guidelines

Revised guidelines for the management of atrial fibrillation include new sections on dronedarone and aspirin–clopidogrel therapy, but dabigatran treatment is slated for an upcoming partial revision, according to the document.[1][1] The document was developed for the American College of Cardiology

Platelet Aggregation and Recruitment with Aspirin-Clopidogrel Therapy

Background: Aspirin-clopidogrel combination therapy inhibits platelet aggregation. The effect on platelet recruitment is unknown. Methods: Thirty chronic ischemic stroke patients taking aspirin alone followed by aspirin-clopidogrel combined therapy had platelet reactivity tests performed over 3 months: ex vivo platelet aggregation, platelet recruitment and urinary 11-dehydro-thromboxane B₂ (11-dhTxB₂)excretion. Statistical analysis of variance compared platelet aggregation and recruitment between aspirin alone and aspirin-clopidogrel, and longitudinal regression analysis estimated platelet recruitment over time. Nonlinear mapping defined variable connections in each patient. Results: Statistically significant differences were found between aspirin alone and aspirin-clopidogrel for (1) adenosine-diphosphate- and collagen-induced platelet aggregation and maximum inhibition of platelet recruitment and (2) increasing inhibition of platelet recruitment over time. Urinary 11-dhTxB₂ excretion did not predict platelet aggregation response. Nonlinear mapping showed patient-unique variable interconnections. Conclusions: Platelet inhibition with aspirin-clopidogrel may increase over time, and future studies should focus on this finding in the context of vascular complications.

Late coronary thrombosis after drug-eluting stent: stent vs patient-driven prescription of aspirin-clopidogrel combination

Introduction Combination therapy with a thienopyridine (ticlopidine or clopidogrel) plus aspirin has emerged as standard care after percutaneous coronary intervention (PCI) with stent implantation. However, the optimal duration of this combined treatment after PCI, originally given for one month after stenting, remains uncertain. Drug-eluting stents (DES) (2-4) reduce intimal hyperplasia and restenosis, but also inhibit stent reendothelization, making the vascular surface more thrombogenic for longer time periods. This has reproposed the issue of the optimal duration of aspirin-clopidogrel therapy. Stent thrombosis with DES occurs with a rate of =1% at 9 months (2-4). However, its late occurrence during post-marketing surveillance, and the extreme severity of ensuing clinical consequences recently prompted the American Food and Drug Administration to release a public warning on this issue. . . .

Aspirin “failures,” clopidogrel added to aspirin, and secondary stroke prevention in veterans presenting with TIA or mild-to-moderate ischemic stroke

Our objective was to investigate whether clopidogrel added to low-dose aspirin reduced vascular events in male patients at our VA hospital who had “failed” aspirin therapy because of a mild-to-moderate stroke or a transient ischemic attack. Of 179 consecutive patients who both reported daily aspirin usage at the time of their newest ischemic event as well as were then operationally defined as aspirin “failures,” 134 (group A) were treated with combined aspirin-clopidogrel, 15 (group B) underwent an early arterial procedure, 25 (group C) were anticoagulated, and 5 were not entered or continued because of either non-compliance or a refusal to participate. Study therapies were modified because of a vascular event in 4.5% of group A (one non-fatal ischemic stroke, one non-fatal myocardial infarction, and four transient ischemic attacks) and 33% of group B (one non-fatal ischemic stroke, one non-fatal myocardial infarction, and three transient ischemic attacks). No major or fatal bleeding events occurred in any of those on combined aspirin-clopidogrel therapy, with minor bleeding in 10 of 134 (7.5%) and 2 of 15 (13.3%) of group A and B patients, respectively. Patients were followed for 18 ± 9.7 months. Combined aspirin-clopidogrel therapy appears both safe as well as effective in this single-center, observational study. Copyright © 2003 by National Stroke Association

A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation

ObjectivesThis study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin. BackgroundDose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. MethodsWe randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. ResultsPretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p < 0.001), enhanced plasma levels of soluble P-selectin (p < 0.001) and had no significant effect on platelet aggregation. Aspirin-clopidogrel combination therapy made no difference to the plasma markers of thrombogenesis or platelet activation (all p = NS), but the platelet aggregation responses to adenosine diphosphate (p < 0.001) and epinephrine (p = 0.02) were decreased. ConclusionsAspirin-clopidogrel combination therapy failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.