Therapeutic Benefit: Aspirin Revisited in Light of the Introduction of Clopidogrel
Abstract & commentary
Source: Gorelick PB, et al. Therapeutic benefit: Aspirin revisited in light of the introduction of clopidogrel. Stroke 1999;30:1716-1721.
Aspirin is currently the standard of care for stroke prevention in patients with identified atherothrombotic disease. Ticlopidine (Ticlid), a potentially more efficacious drug than aspirin, has been available as alternative therapy, but serious side effects such as neutropenia limit its usefulness. Now, clopidogrel (Plavix), a thienopyridine derivative similar to ticlopidine, offers similar efficacy, with fewer side effects.
Clopidogrel was recently compared with aspirin in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. Among patients with recent MI, stroke, or significant peripheral vascular disease, CAPRIE found an event rate of 5.83 events per year in the aspirin-treated groups vs. 5.32 events per year in the clopidogrel-treated group (P = 0.043), an 8.7% relative risk reduction. CAPRIE used a combined end point of ischemic stroke, MI, or vascular death.
A secondary subgroup analysis in CAPRIE showed that not all patients benefited equally. The largest benefit of clopidogrel, accounting for 75% of its therapeutic advantage, occurred in the group with peripheral arterial disease. The relative risk reduction in these patients was 23.8% compared to 7.3% for those with stroke (95% CI-5.7-18.7; P = 0.26, a nonstatistically significant difference).
Gorelick and colleagues review the safety profiles of clopidogrel compared with aspirin. Clopidogrel does not cause significant neutropenia, although long-term data are not available for this drug. Observations are limited to three years. By contrast, aspirin has been in use for more than 100 years. The CAPRIE study used 325 mg of plain aspirin. Enteric-coated aspirin (the most commonly prescribed form) or low-dose aspirin (probably of equal efficacy) may have compared even more favorably with clopidogrel.
Clopidogrel is considerably more expensive than aspirin (45-fold cost differential) and remains 5- to 7-fold more costly when costs to prevent an event or save a life are calculated. Patient compliance may also be influenced by the higher drug cost of clopidogrel.
Analyzing efficacy, safety, and cost, Gorelick et al conclude that aspirin should remain first-line therapy in this setting. As Gorelick et al observe, however, clopidogrel is a viable alternative, particularly for patients who fail aspirin or cannot tolerate it. —azs (Dr. Alan Z. Segal is Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Hospital.)