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Antithrombotic Secondary Prevention After Stroke
Hans-Christoph Diener1, Peter Ringleb
1*Department of Neurology, University of Essen, Hufelandstrasse 55, Essen 45122, Germany. h.deiner@uni.essen.de
Insights
Antiplatelet drugs significantly reduce stroke risk in TIA and ischemic stroke patients. Aspirin, dipyridamole, ticlopidine, and clopidogrel offer varying benefits and side effect profiles for secondary stroke prevention.
Area of Science:
- Neurology
- Cardiology
- Pharmacology
Background:
- Transient ischemic attack (TIA) and ischemic stroke patients benefit from antiplatelet therapy.
- Antiplatelet agents reduce stroke, myocardial infarction (MI), and vascular death risk.
Purpose of the Study:
- To review the efficacy and safety of antiplatelet drugs for secondary stroke prevention.
- To compare aspirin, dipyridamole, ticlopidine, and clopidogrel in stroke prevention.
Main Methods:
- Review of clinical trials and guidelines on antiplatelet therapy for TIA and ischemic stroke.
- Analysis of drug efficacy, side effect profiles, and optimal dosing.
Main Results:
- Aspirin (50-325 mg) moderately reduces stroke, MI, and vascular death; low doses are better tolerated.
- Aspirin plus dipyridamole is superior to aspirin alone for stroke prevention.
- Clopidogrel offers a better safety profile than ticlopidine, which is reserved for aspirin-intolerant patients.
Conclusions:
- Antiplatelet therapy is crucial for secondary stroke prevention.
- Drug selection depends on patient tolerance, risk factors, and previous events.
- Further research is needed for optimal management of patients already on aspirin or with recurrent events.
Abstract:
In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in term of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some endpoints, it is superior to aspirin. Due to its side effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 can not be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.