Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI.

2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat.

There were no drop-outs. 59 (4·5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6·4%) in the placebo group (relative risk 0·70 [95% CI 0·50–0·97], p=0·03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0·03), and of cardiovascular death or myocardial infarction (p=0·047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0·002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0·001). At follow-up, there was no significant difference in major bleeding between the groups (p=0·64).

In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.