Boston, MA - The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial has been published in the August 16, 2001 issue of the New England Journal of Medicine.1 The results, which were presented and discussed at length at the American College of Cardiology meeting in March 2001, showed a significant reduction in ischemic events with clopidogrel in unstable angina patients at the expense of an increase in bleeding.

The trial randomized 12562 patients within 24 hours of the onset of unstable angina symptoms to clopidogrel or placebo for 3 to 12 months. All patients received aspirin. There were two primary endpoints, both of which were reduced significantly with clopidogrel:

Clopidogrel was associated with a significant increase in major bleeding, but life-threatening bleeding was not significantly increased:

The authors, led by Dr Salim Yusuf (McMaster University, Hamilton, ON), note that this study primarily involved centers that did not routinely conduct early invasive procedures as such a policy would have led to a high rate of immediate discontinuation of study medication and use of open-label clopidogrel. However, 16.5% and 21.2% of patients respectively did undergo CABG or PTCA at some point, and in around 85% of these, the study medication was temporarily interrupted for more than 5 days. The vast majority of patients who underwent PTCA received clopidogrel or a similar thienopyridine antiplatelet agent for 2-4 weeks. In patients who underwent CABG, the study medication was restarted after a median of 11 days.

The researchers point out that the benefits of clopidogrel were seen both in those patients undergoing revascularization procedures and those who were not. The results in the PTCA patients are the subject of another paper (PCI-CURE), which is published in this week's Lancet, and will be reported by theheart.org when the embargo lifts later today.

The benefits were also observed in patients at high, medium or low risk of cardiovascular events and in those receiving various proven therapies, such as aspirin, lipid-lowering drugs, ACE inhibitors and -blockers, the authors add.

The excess risk of bleeding is similar to that observed with aspirin alone.

In terms of bleeding, the researchers say that for every 1000 patients treated with clopidogrel, 6 will require a transfusion, but there was no increase in bleeding that caused strokes or permanent disability or required surgical intervention or inotropic agents.

?Furthermore the excess risk of bleeding we observed is similar to that observed with aspirin alone, as compared with a control, in previous studies and lower than that observed in most trials of the short-term intravenous use or prolonged oral use of glycoprotein IIb/IIIa receptor inhibitors," the authors note. However, they add that the risk of bleeding may have been partly mitigated by the temporary discontinuation of the study medication before surgery.