Easton JD. Clinical aspects of the use of clopidogrel, a new antiplatelet agent. Seminars in Thrombosis & Hemostasis. 25 Suppl 2:77-82, 1999.
Clopidogrel, a new platelet ADP receptor antagonist, is more effective than aspirin in reducing the risk of subsequent vascular ischemic events in patients with a broad spectrum of symptomatic atherosclerosis (recent ischemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease). In CAPRIE (clopidogrel versus aspirin in patients at risk of ischemic events), a randomized, blinded, active control trial in 19,185 high-risk patients, clopidogrel reduced the combined risk of ischemic stroke, myocardial infarction or vascular death by 8.7% compared with aspirin (p = 0.043). The CAPRIE cohort had a mean age of 62.5 years, which was reflected in the high proportion of patients who had medical conditions other than symptomatic atherosclerosis, and in the extensive use of concurrent therapies, including commonly used cardiovascular drugs. For all concomitant medications analysed, there was no evidence of statistically or clinically significant interactions with clopidogrel. The CAPRIE data confirm the findings of earlier clinical studies, which suggested that clinically significant drug interactions with clopidogrel are rare, that it can safely be prescribed with a range of other drugs (including phenobarbital, cimetidine, estrogen, digoxin, theophylline, atenolol, nifedipine, or nifedipine-atenolol in combination), and that the clinically proven dose of 75 mg once daily is suitable for all age groups studied. Moreover, CAPRIE demonstrated that there is no need for an adjustment of clopidogrel dose on the basis of gender, weight or race, and that there is no need for routine hematological monitoring. Additional clinical pharmacology studies have shown that the absorption of clopidogrel is unaffected by food or antacids, and that no dose adjustment is necessary in patients with renal impairment or with mild-to-moderate hepatic impairment. Due to pharmacologic considerations and limited clinical data, clopidogrel should be used cautiously with heparin, warfarin or non-steroidal anti-inflammatory drugs. With a simple regimen of 75 mg once daily indicated for all patients, clopidogrel combines a favorable risk/benefit ratio with ease of use in clinical practice.