Insights from CURE: Using Clopidogrel on Top of Standard Therapy

The principal pathophysiological mechanism in patients with unstable angina pectoris (UAP) and non-Q-wave myocardial infarction (NQMI) is atherothrombosis--the formation of a platelet-rich thrombus at the site of a disrupted or eroded atherosclerotic plaque. Despite standard therapy, which includes intravenous heparin or low-molecular-weight heparin and acetylsalicylic acid (ASA) during the acute phase followed by ASA on a long-term basis, the prognosis for patients remains poor. The efficacy of early and long-term treatment with clopidogrel (clopidogrel bisulphate) on top of standard therapy including ASA has recently been tested in patients with UAP and NQMI. In the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischaemic Events) Trial, more than 12,500 patients were randomized, in a double-blind manner, to receive placebo or clopidogrel, given as an initial 300-mg loading dose, followed by a 75-mg daily dose. All patients received a recommended dose of ASA (75-325 mg daily). The mean duration of treatment and follow-up was 9 months (minimum 3 months, maximum 12 months). CURE clearly showed that clopidogrel reduced the risk of a composite of cardiovascular death, stroke and MI, with a relative risk reduction of 20% (95% confidence interval, 72-90%; p < 0.001). The protective effect of clopidogrel was apparent within 2 h of initiation of therapy, and the benefit was consistent at 30 days and after long-term treatment. The benefit of clopidogrel was observed across the spectrum of high- and low-risk patients and was obtained with an acceptable risk of bleeding and no increase in intracranial haemorrhage. Based on data from CURE, the use of clopidogrel on top of standard therapy including ASA can be expected to become the new foundation therapy in patients with UAP and NQMI.