Clopidogrel Plus Aspirin Versus Warfarin in Patients With Stroke and Aortic Arch Plaques

Abstract

Retrospective, unblinded, nonrandomized comparisons between these 2 strategies have been inconclusive 13 and no randomized evaluation of these strategies has been conducted.14 We hypothesized that the combination of aspirin plus clopidogrel was 25% superior to dose-adjusted warfarin on prevention of new vascular Background and Purpose-Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. Methods-This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta >4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. Results-The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups. Conclusions-Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235248.

Prevalence of Positive Troponin and Echocardiogram Findings and Association With Mortality in Acute Ischemic Stroke

“…14 Aortic arch atheromas greater than 4mm are an indicator of vascular disease, but because treatment with anticoagulation has not been shown to reduce vascular event rates we did not include them on the basis that their presence does not alter management. 15 In contrast we did include spontaneous echo contrast or “smoke” due to its strong association with suspected atrial thromboembolism as a cause of stroke. 21 …”

Cardioembolic Stroke

“…32 In clinical practice, aortic atheromas may be an under-recognized cause of stroke because the imaging modalities required to detect them, such as transesophageal echocardiography, are not routinely performed in stroke patients. 33 Early reports suggested a very high rate of stroke recurrence (12% per year) in patients with aortic arch atheromas, 34 but a more recent trial found a much lower rate (<3% per year), 35 suggesting that secular trends in the treatment of atherosclerotic risk factors may be reducing the contribution of aortic atherosclerosis to the burden of stroke.…”

“…However, given their manifest atherosclerotic disease, these patients stand to benefit from general recommendations regarding primary prevention of stroke. 122 Data on therapies to prevent recurrent stroke in patients with aortic atherosclerosis 35 will be discussed in a separate section of this Compendium (see section on “Cryptogenic Stroke”).…”

Dual Antiplatelet Therapy of Clopidogrel and Aspirin in Secondary Prevention of Ischemic Stroke: Evidence and Indications

“… FASTER, The Fast Assessment of Stroke and TIA to prevent Early Recurrence ; CHANCE, Clopidogrel in High‐risk patients with Acute Non‐disabling Cerebrovascular Events ; WASID, Warfarin‐Aspirin Symptomatic Intracranial Disease ; SAMMPRIS, Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis ; CARESS, Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis ; CLAIR, CLopidogrel plus Aspirin for Infarction Reduction in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals ; ARCH, Aortic Arch Related Cerebral Hazard ; SPAF, Stroke Prevention in Atrial Fibrillation ; ACTIVE, Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events ; PCI‐CURE, Percutaneous Coronary Intervention‐Clopidogrel in Unstable Angina to Prevent Recurrent Events ; CREDO, Clopidogrel for the Reduction of Events During Observation ; DAPT, 12 or 30 months of Dual Antiplatelet Therapy after Drug‐Eluting Stents ; CUREs, Clopidogrel in Unstable Angina to Prevent Recurrent Events . …”

“…There were similar risks of major hemorrhage between both groups. Because of 33 primary outcomes below expectations and long duration of recruitment (8.25 years), this trial lacked statistical power . But in consideration of increasing risks of vascular deaths with well‐conducted warfarin therapy and the complexity of INR‐adjusted dosing, the antiplatelet strategy of DAPT for 90 days and clopidogrel monotherapy for long‐term use may be more advisable in clinical practice.…”