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Clopidogrel for cerebrovascular prevention
1Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Insights
Clopidogrel demonstrated an 8.7% reduction in vascular events compared to aspirin in high-risk patients. While effective, clopidogrel
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Neurology
Background:
- Atherothrombosis underlies ischemic stroke, myocardial infarction, and peripheral arterial disease.
- Antiplatelet agents like aspirin and ticlopidine are used for secondary prevention of vascular events.
- Newer antiplatelet agents are needed due to potential adverse effects of existing therapies.
Purpose of the Study:
- To compare the efficacy and safety of clopidogrel versus aspirin in patients at risk of ischemic events.
- To evaluate clopidogrel's effectiveness in reducing the composite outcome of ischemic stroke, myocardial infarction, or vascular death.
Main Methods:
- The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial was a randomized, blinded, international study.
- 19,185 patients were enrolled in an intention-to-treat analysis.
- Compared the incidence of ischemic stroke, myocardial infarction, or vascular death between clopidogrel and aspirin groups.
Main Results:
- Clopidogrel showed an 8.7% relative risk reduction in the composite outcome compared to aspirin (p = 0.043).
- Annual event rates were 5.33% for clopidogrel and 5.83% for aspirin.
- Adverse events were generally higher with aspirin, except for rash, diarrhea, and abnormal liver function.
Conclusions:
- Clopidogrel offers comparable efficacy to aspirin with a potentially better safety profile, suggesting it may replace ticlopidine for stroke prevention.
- Clopidogrel's higher cost and less widespread experience may limit its adoption over aspirin as first-line therapy for some clinicians.
- The CAPRIE study demonstrated a significant advantage for clopidogrel over aspirin, leading some clinicians to prefer it as a first-choice treatment.
Abstract:
Ischemic stroke, myocardial infarction and peripheral arterial disease are different clinical manifestations commonly due to the same underlying disease, i.e. atherosclerosis with subsequent thrombosis/embolism (atherothrombosis). Many clinical trials of secondary prevention after stroke or TIA have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of subsequent vascular events. Aspirin and triclopidine have been shown to be effective in placebo-controlled studies for the composite outcome of stroke, myocardial infarction, or vascular death. Contrasting with these benefits, there were potentially serious, though rare, adverse effects. These considerations certainly justify the development of new antiplatelet agents. Clopidogrel is a new ADP-receptor antagonist, with a greater activity in animal models of thrombosis. CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) was a randomized, blinded, international trial designed to assess the relative efficacy of clopidogrel and aspirin in reducing the risk of the outcome cluster of ischemic stroke, myocardial infarction, or vascular death, as well as to assess their relative safety. 19,185 patients were recruited. The intention-to-treat analysis showed that the relative risk reduction was 8.7% (95% CI 0.3-16.5, p = 0.043) in favor of clopidogrel from an overall annual event rate of ischemic stroke, myocardial infarction, or vascular death, ranging from 5.83% in the aspirin group to 5.33% in the clopidogrel group. The percentage of adverse events reported was higher in the aspirin group for all categories except rash, diarrhea, and abnormal liver function. It seems likely that clopidogrel will replace ticlopidine for stroke prevention, because of its better safety profile, and comparable efficacy. Clopidogrel probably will not replace aspirin as the first line therapy for many clinicians because of its higher cost and lack of widespread experience. However, other clinicians have already decided that they will use clopidogrel as first choice, because of the significant advantage over aspirin demonstrated in the CAPRIE study.