Long-Term Therapy to Prevent Stroke

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Figure 1.
Overlap of atherosclerotic disease.14
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Figure 2.
Efficacy of long-term clopidogrel or aspirin therapy in patients with >1 previous acute ischemic event based on 1-year and 3-year event rates for 2 composite endpoints.45 The overall relative risk reduction for clopidogrel versus aspirin was 14.9% (P = .045) for the endpoint of ischemic stroke (IS), myocardial infarction (MI), and vascular death (VD) and 12.0% (P = .039) for IS, MI, and rehospitalization.

Table 1.

Modifiable Risk Factors for Stroke20,21

Risk Factor

Hypertension

Smoking (including passive smoking)

Diabetes

Asymptomatic carotid stenosis

Increased blood lipid levels

Atrial fibrillation (nonvalvular)

Obesity

Physical inactivity

Excess alcohol intake

Table 2.

Trials Involving Clopidogrel Combination Therapies That Are in Progress*

Trial	Details
CHARISMA	Investigating the effects of adding clopidogrel 75 mg/day to low-dose aspirin (75 to 162 mg) in patients at high risk of developing atherothrombotic events.49 Completed in July 2005; results pending.
SPS3	Investigating the effects of aspirin 325 mg/day or aspirin 325 mg/day + clopidogrel 75 mg/day in the prevention of secondary stroke, major vascular events, and cognitive decline among patients with small subcortical strokes.
	This study is also comparing a standard (130 to 149 mm Hg systolic) blood pressure against an aggressive (<130 mm Hg systolic) blood pressure target, and it is evaluating cognitive status in addition to recurrent stroke as an endpoint.
PRoFESS	This study compares clopidogrel (± telmisartan) therapy with aspirin + dipyridamole (± telmisartan) for secondary stroke prevention.
FASTER	The trial will involve patients randomized to receive clopidogrel (or placebo) and simvastatin (or placebo) within 12 hours of onset of TIA or minor stroke; all patients will receive aspirin.
	The only clinical stroke trial to include a loading dose of clopidogrel, as was used in the CURE acute coronary syndrome trial.

* Updates on these trials are available online at: http://www.strokecenter.org/trials.

Table 3.

Incidence of Adverse Events in Patients Treated with Clopidogrel or Aspirin4

	Adverse Event (Percentage of Patients)
	Clopidogrel	Aspirin
Rash	6.0	4.6^*
Diarrhea	4.5	3.4^*
Indigestion/nausea/vomiting	15.0	17.6^*
Any bleeding disorder	9.3	9.3
Intracranial hemorrhage	0.4	0.5
Gastrointestinal hemorrhage	2.0	2.7^*
Abnormal liver function	3.0	3.2^*