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 terms 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 end points, 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 cannot 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.