Double antiplatelet Rx:
• Combination pf clopidogrel + Aspirin vs aspirin alone had a significantly increased annual rate of both major hemorrhage (2.1 versus 1.1 percent) and all-cause mortality (2.1 versus 1.4 percent)
• Furthermore, treatment with combination compared with aspirin alone did not reduce the risk of recurrent stroke.
A summary of trials:
• 7599 patients with stroke or TIA plus risk feature,
• randomly assigned to clopidogrel (75 mg daily) plus aspirin (75 mg daily) versus clopidogrel (75 mg daily) alone.
• Follow-up was 18 months.
• double agents did not reduce the risk of major vascular eventsHas
• significant increase in life-threatening bleeding complications, mainly intracranial and gastrointestina
• lOver 18-month, increase of 1.3 percent for life-threatening hemorrhage
• aspirin plus clopidogrel versus aspirin alone
• 15,603 patients with either documented cardiovascular disease (coronary, ischemic cerebrovascular, or peripheral arterial) or, in 21 percent of patients, multiple atherothrombotic risk factors (eg, diabetes, hypertension, primary hypercholesterolemia, current smoking, asymptomatic carotid stenosis)
• Double angents did not reduce the risk of the composite primary end point (MI, stroke of any cause, or death from cardiovascular causes) compared with aspirin alone (6.8 versus 7.3 percent)
• Double agent: significant increase in moderate bleeding (2.1 versus 1.3 percent) and a nonsignificant increase in severe bleeding (1.7 versus 1.3 percent)
• over 3000 patients with subcortical (ie, lacunar) stroke confirmed by MRI
• combination of aspirin plus clopidogrel versus aspirin alone was terminated before completion because of a higher frequency of bleeding events (mostly systemic) and a higher mortality rate in patients on dual antiplatelet therapy
Two small trials
CARESS and CLAIR: of patients with recently symptomatic large artery stenosis found that, compared with aspirin alone, early treatment with aspirin plus clopidogrel reduced the number of microembolic signals detected on transcranial Doppler ultrasound.
However, whether this surrogate measure would translate into clinical benefit for patients with symptomatic large artery stenosis remains uncertain.