While a subset of patients may experience aspirin resistance, reliable assays in clinical practice are not commonly available to guide management. Current recommendations suggest that use of between 50 mg and 325 mg of aspirin is appropriate for secondary prevention.7
Clopidogrel is another antiplatelet agent that can be given daily at 75 mg as alternate therapy for secondary prevention of non-cardioembolic stroke. The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events trial comparing clopidogrel with aspirin in patients at risk of ischemic events demonstrated significant reduction in the annual rate of combined endpoint of stroke, myocardial infarction, and vascular death—from 5.83% with aspirin to 5.32% with clopidogrel.8 This study’s applicability to secondary prevention of stroke is limited by the fact that only 19% of the patients in this trial were included because of prior stroke, and the results were not significant for reduction of stroke as a lone endpoint. Clopidogrel is recommended as an acceptable agent for CVA secondary prevention and is preferred for patients with stroke and an aspirin allergy or with recent coronary stent.
The combination of a low-dose aspirin and extended-release dipyridamole has proved superior to aspirin monotherapy in multiple trials. Over two years, the European Stroke Prevention 2 trial found an 18% reduction with aspirin alone compared with 37% reduction with the combination therapy, and the European/Australasian Stroke Prevention in Reversible Ischaemia trial confirmed that the combination reduced the absolute rate of second ischemic events by 1% annually.9-10 Headache is a common side effect of dipyridamole and may limit use. Dypridamole/aspirin is recommended as another acceptable option for secondary prevention of non-cardioembolic stroke.
Evidence suggests that aspirin/dipyridamole and clopidogrel—although significantly more expensive—are more effective than aspirin monotherapy for preventing second cerebral ischemic events. Direct comparison between aspirin/dipyridamole and clopidogrel is ongoing in the Prevention Regimen for Effectively Avoiding Second Stroke trial, with results anticipated in 2008.
Things That Don’t Work
The Warfarin-Aspirin Recurrent Stroke Study trial demonstrated that warfarin was not better than aspirin for prevention of non-cardioembolic stroke, and the Warfarin–Aspirin Symptomatic Intracranial Disease trial found the same result for patients with intracranial stenosis.11-12 There is little evidence that warfarin should have a role in the treatment of most non-cardioembolic strokes. The MATCH trial failed to show benefit to adding aspirin to clopidogrel over clopidogrel monotherapy for secondary preventions of non-cardioembolic cerebral ischemia.13 Despite efficacy following coronary stenting, the combination of clopidogrel and aspirin can not be recommended for stroke prevention.
What To Do
Aggressive risk factor modification is key in the prevention of second ischemic events. One of the most promising therapies is the use of statins following a CVA. Maintaining low-density lipoprotein (LDL) at less than 100 mg/dL (or less than 70 mg/dL in the highest-risk patients) is recommended despite a relatively weak association between stroke and hyperlipidemia.
This stands in contrast to the strong relationship between elevated LDL and coronary disease. However, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial utilized high-dose atorvastatin after acute CVA and was able to create an absolute risk reduction for second stroke of 2.2% over the next five years.14 It is possible that the findings of this trial may reflect actions of statin therapy on the endothelium independent of the lipid lowering effect.
Blood pressure commonly has a transient elevation following cerebral ischemia. This is managed permissively to preserve perfusion to the ischemic penumbra. Once the hyperacute period is over, reduction of blood pressure to less than 140/90 mm/Hg (130/80 mm/Hg for diabetics) is recommended.