Ischemic stroke clopidogrel

The CAPRIE trial found that compared to aspirin (325 mg daily), clopidogrel (75 mg daily) was associated with RRR of 8.7% p = 0.043) for the composite endpoint of ischemic stroke, Ml, or vascular death among 19,185 subjects with stroke, MI, or peripheral arterial disease, but no significant reduction in the composite endpoint in the subgroup with stroke (RRR 7.3%, p = 0.26). No comparison of clopidogrel with aspirin in the acute stroke period was performed. Furthermore, stroke as an endoint was not significantly reduced in the stroke patients entered in this trial (RRR 8.0%, p = NS). 

Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH) randomised, double-blind, placebo-controlled trial. Lancet 2004 364(9431) 331-337. 

Recent Ml or stroke, or established peripheral arterial d/sease For patients with a history of recent Ml, recent stroke, or established peripheral arterial disease, clopidogrel has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new Ml (fatal or not), and other vascular death. 

The results showed that patients treated with clopidogrel had an annual 5,32% risk of ischemic stroke, Ml, or vascular death compared with 5,83% with aspirin (RRR = 8.7% in favor of clopidogrel, P = 0,045). There were no major differences in terms of safety. 

In the CAPRIE trial (Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events), clopidogrel reduced the risk of Ml, stroke, or vascular death by 23.8% compared with aspirin in patients with PAD (48). Although this is an impressive reduction in major events, the benefits of clopidogrel over aspirin were identified as a subgroup analysis rather than a primary endpoint. 

There is no clear evidence that any particular dose of aspirin is more effective than others. However, the symptoms of aspirin toxicity, such as dyspepsia and constipation, are dose related, so the smallest effective dose should be used. A starting dosage of 150-300 mg per day is advised for the acute phase of ischemic stroke followed by longterm treatment with 75-150 mg per day. Patients intolerant of aspirin should be treated with clopidogrel if available, or if not with dipyridamole. These newer agents cost significantly more than aspirin. The use of combination antiplatelet therapy is discussed further in Ch. 24. 

Antiplatelet therapy reduces the risk of recurrent vascular events after TIA and ischemic stroke, although few trials have distinguished between different etiological subtypes (Antithrombotic Trialists Collaboration 2002). Most trial data concern aspirin, but other antiplatelet agents such as clopidogrel (CAPRIE Steering Committee 1996) or extended-release dipyridamole (Sivenius et al. 1991) have also been shown to be effective although mechanisms of action may differ (Table 24.2). 

Clopidogrel MATCH Clopidogrel versus aspirin plus clopidogrel within six months of ischemic stroke or TIA... 

CHARISMA Aspirin versus aspirin plus clopidogrel in patients with cardiovascular disease or multiple risk factors (including ischemic stroke)... 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, clopidogrel, and extended-release dipyridamole plus aspirin are aU considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopidogrel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

Ischemic stroke TPA, heparin, ASA, clopidogrel, ticlopidine, dipyridamole and aspirin, warfarin, surgery Neurological worsening, bieeding, PT/APTT, INR, CBC... 

All patients who have had an acute ischemic stroke or TEA should receive long-term antithrombotic therapy for secondary prevention. In patients with noncardioembolic stroke, this will be some form of antiplatelet therapy. In a recent meta-analysis, the overall benefit of antiplatelet therapy in patients with atherothrombotic disorders was estimated to be 22%. Aspirin is the best-studied of the available agents and, until recently, was considered the sole first-line agent. However, published literature has supported the use of clopidogrel and the aspirin plus extended-release dipyridamole combination product (ERDP + ASA) as additional first-line agents in secondary stroke prevention. 

Clopidogrel and ticlopidine are effective in preventing transient ischemic attacks and ischemic strokes, especially in patients who cannot tolerate aspirin. These drugs prevent thrombosis in patients who have recently received a coronary artery stent. 

The CAPRIE trial (68) clopidogrel vs aspirin in patients at risk of ischemic events compared the efficacy of clopidogrel (plavix) to aspirin in more than 19,000patients with atherosclerosis manifested as ischemic stroke, MI, or LEAD defined by an ABI of 0.85 or less, history of revascularization or amputation secondary to ischemia. In the CAPRIE trial, there were more than 6400 patients with LEAD. Clopidogrel was associated with an overall relative risk reduction of 8.7% for adverse cardiovascular events. Patients with LEAD received the greatest benefit, with a relative risk reduction of 23.8% compared to aspirin alone (68). 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

The FASTER randomized controlled pilot trial studied the benefit of clopidogrel versus placebo and simvastatin versus placebo initiated within 24-hours of symptom onset in patients with TIA or minor stroke, all of whom were treated with aspirin (Kennedy et al. 2007). The primary outcome was any stroke (ischemic and hemorrhagic) within 90 days. Minor stroke was defined as a score < 3 on the National Institutes of Health Stroke Scale (NIHSS) at the time of randomization and TIA was defined in the usual way. In addition, patients were excluded if they did not have weakness or speech disturbance or if symptom duration was less than five minutes. 

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