Stroke antiplatelet therapy

Antiplatetelet Trialists Collaboration (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324 71-86... 

Combination Anticoagulant and Antiplatelet Therapy in Acute Stroke... 

Finally, a Cochrane review of antiplatelet therapy following CEA found no evidence of a difference in mortality when antiplatelets were compared with placebo. However, treatment with antiplatelet agents following CEA decreased the risk of postoperative stroke (OR 0.58, 95% Cl 0.34-0.98). ... 

Antiplatelet Trialist Collaboration. Collaborative overview of randomised trials of antiplatelet treatment. Part I prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994 308 81-106. 

Antiplatelet therapy for acute ischemic stroke. The Cochrane review 2003. 

Randomized trials have been completed assessing the role of antiplatelet therapy with aspirin for primary stroke prevention. The use of aspirin in patients with no history of stroke or ischemic heart disease reduced the incidence of non-fatal myocardial infarction (MI) but not of stroke. A meta-analysis of eight trials found that the risk of stroke was slightly increased with aspirin use, especially hemorrhagic stroke. Major bleeding risk was also increased with aspirin use.4 Aspirin is beneficial in the primary prevention of MI, but not for primary stroke prevention. 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

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, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel 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. 

Koudslaal P. Anticoagulants versns antiplatelet therapy foe preventing soroke in patients with nomheumatic atrial fibrillation and a history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 1999. Issne 4. 

The ACC/AHA guidelines state that ASA in daily doses of 75 to 325 mg is recommended as a safe and effective antiplatelet therapy to reduce the risk of Ml, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD (26). 

Another important difference is the extent of the evidence base for treatments in major stroke compared with TIA and minor stroke. The concepts of stroke units and administration of thrombolysis have been researched, developed and implemented since the 1980s for patients with major stroke. Yet, although the concept of TIA arose in the 1950s and treatments such as carotid endarterectomy, anticoagulation, antiplatelet therapy and other risk factor management were subsequently proven effective, it was not until 2007 that the first reports were published on the feasibility and effectiveness of urgent assessment and treatment of TIA in specialist units (Rothwell et al. 2007 Lavallfe et al. 2007). 

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). 

Hgwo 24.1. Proportional effects of antiplatelet therapy on vascular events (myocardial infarction, stroke, or vascular death) in four main high risk categories of trial and in low risk (primary preventim). 

TIA were at much higher untreated risk of a subsequent non-fetal stroke (10.2%) than of a non-fittal MI (2.9%), so that antiplatelet therapy prevented around twice as many non-... 

When antiplatelet therapy is commenced some months after an acute stroke, and continued for several years, the randomized evidence shows that for every 1000 patients treated around 1 serious vascular event is avoided during each mondi of treatment (8). The results of 1ST and CAST show that early treatment prevents around 9 recurrent strokes or deaths per 1000 patients during the first month (48). Moreover, if aspirin is started early then it is more likely to be continued after hospital discharge. Hence aspirin 160-300mg should now be considered as early as possible for almost all patients presenting with acute ischemic stroke, provided that there are no strong contraindications and that hemonhagic stroke can be excluded reliably. 

Overall, antiplatelet therapy produced a 13% (95% Cl 5-20%) proportional reduction in the odds of a vascular event, corre onding to an absolute risk reduction of only about one vascular event avoided per 1000 patients treated per year (Table 24.2 (a)). As in the ofiier low risk trials, the risk of MI was reduced in both TPT and HOT in TPT the rate of all (i.e. fotal or non-fetal) ischemic heart disease was reduced by 20% (95% Cl 1 -35%) and in HOT the rate of all MI was reduced by 36% (95% Cl 15-51%). But, alfiiough antiplatelet therapy appeared to reduce the risk of ischemic stroke, it also appeared to increase the risk of hemonhagic stroke overall in TPT there was a non-significant 3% (95% Cl -45-35%) reduction in the rate of all stroke and in HOT there was a nonsignificant 2% (95% Cl -24-22%) reduction in the rate of all stroke. As in the other low risk trials, there was no overall effect on vascular death or on all-cause mortality (52,53). 

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