Plavix Clinical Pharmacology

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Plavix - Clinical Pharmacology [Clopidogrel]

The CAPRIE trial was a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing PLAVIX (75 mg daily) to aspirin (325 mg daily). The patients randomized had: 1) recent histories of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; or 3) objectively established peripheral arterial disease. Patients received randomized treatment for an average of 1.6 years (maximum of 3 years).

The trial's primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. Deaths not easily attributable to nonvascular causes were all classified as vascular.

Table 1: Outcome Events in the CAPRIE Primary Analysis

PLAVIX aspirin
Patients 9599 9586

IS (fatal or not) 438 (4.6%) 461 (4.8%)
MI (fatal or not) 275 (2.9%) 333 (3.5%)
Other vascular death 226 (2.4%) 226 (2.4%)

Total 939 (9.8%) 1020 (10.6%)

As shown in the table, PLAVIX (clopidogrel bisulfate) was associated with a lower incidence of outcome events of every kind. The overall risk reduction (9.8% vs. 10.64%) was 8.7%, P=0.045. Similar results were obtained when all-cause mortality and all-cause strokes were counted instead of vascular mortality and ischemic strokes (risk reduction 6.9%). In patients who survived an on-study stroke or myocardial infarction, the incidence of subsequent events was again lower in the PLAVIX group.

The curves showing the overall event rate are shown in Figure 1. The event curves separated early and continued to diverge over the 3-year follow-up period.

Figure 1: Fatal or Non-Fatal Vascular Events in the CAPRIE Study

Although the statistical significance favoring PLAVIX over aspirin was marginal (P=0.045), and represents the result of a single trial that has not been replicated, the comparator drug, aspirin, is itself effective (vs. placebo) in reducing cardiovascular events in patients with recent myocardial infarction or stroke. Thus, the difference between PLAVIX and placebo, although not measured directly, is substantial.