Section C: Clinical trial update: Oral antiplatelet therapy CURE: Long-term reduction in primary outcome with clopidogrel Content Points: The CURE study (Clopidogrel in Unstable angina to prevent Recurrent Events) was an evaluation of clopidogrel when added to aspirin therapy in 12,562 patients with non–ST-elevation ACS.12 – Patients were randomized to clopidogrel (300-mg loading dose, followed by 75 mg daily) or placebo – All patients continued or were started on aspirin 75 to 325 mg daily The primary outcome was combined cardiovascular death, nonfatal MI, and stroke. As shown, there was a 20% reduction in risk of the primary outcome at 1 year (relative risk, 0.80; 95% CI, 0.72 to 0.90; P < 0.001).11 The primary outcome rate was 9.3% in the clopidogrel group and 11.4% in the placebo group.

CURE: Bleeding complications Content Points: In the CURE study, risk of major bleeding was increased among clopidogrel patients.12 – Major bleeding occurred in 3.7% and 2.7% of clopidogrel and placebo patients, respectively (relative risk, 1.38; 95% CI, 1.13 to 1.67; P = 0.001) Life-threatening bleeding was not significantly more common in the clopidogrel group compared with the placebo group (2.2% vs 1.8%). However, non–life-threatening bleeding was significantly more common (1.5% vs 0.9%, P = 0.002). The CURE investigators concluded that clopidogrel reduced the risk of the primary outcome, but that clinical benefit was accompanied by an increased risk of bleeding.

PCI-CURE: Reduction in CV death or MI with clopidogrel Content Points: In a cohort of 2658 patients in CURE, percutaneous coronary intervention (PCI) was carried out (the PCI-CURE substudy).13 The primary outcome in this substudy was cardiovascular death, nonfatal MI, or urgent target-vessel revascularization at 30 days. On randomization, all patients assigned to clopidogrel received a 300-mg loading dose. Open-label thienopyridine (clopidogrel or ticlopidine) prior to PCI was permitted in those patients for whom stenting was expected; 24.7% of placebo patients received a thienopyridine prior to PCI. Following PCI, open-label thienopyridine was also given to all stented patients for 2 to 4 weeks, after which placebo or clopidogrel (75 mg) was resumed. – 84.1% of placebo patients and 82.9% of clopidogrel patients received thienopyridine in this manner Clopidogrel produced a 30% reduction in risk of the primary outcome at 30 days (relative risk, 0.70; 95% CI, 0.50 to 0.97; P = 0.03). – The primary outcome rate was 4.5% in the clopidogrel group and 6.4% in the placebo group; this difference was attributed to the clopidogrel loading-dose As shown, when all primary outcome events before and after PCI were included, there was a 31% risk reduction in cardiovascular death or nonfatal MI (relative risk, 0.69; 95% CI, 0.54 to 0.87; P = 0.002). This finding supported long-term use of clopidogrel. The trial investigators concluded that, in patients with non–ST-elevation ACS who are scheduled for PCI, pretreatment with aspirin and clopidogrel followed by long-term therapy reduces major cardiovascular events.