CURE trial

• the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) has examined whether the addition of clopidogrel improves outcomes in this setting
  • prospective, placebo-controlled, randomised
  • more than 12,500 patients presenting with non-ST elevation acute coronary syndrome - almost all patients manifested some ECG abnormallity or raised concentrations of serum markers for myocardial injury
  • exclusion criteria included contraindications to antithrombotic or antiplatelet therapy, a high risk of bleeding, or severe heart failure
  • study continued for a mean duration of 9 months
  • patients not already on aspirin were given this drug after randomisation; in addition patients were randomised to receive either clopidogrel (300mg loading dose followed by a maintenance dose of 75 mg daily) or matching placebo for 3-12 months (mean 9 months)
  • outcomes:
    • clopidogrel was associated with a lower rate of a composite endpoint of cardiovascular death, myocardial infarction or stroke - 9.3% instead of 11.3% (relative risk 0.80, 95% CI 0.72-0.89) - this finding seemed consistent across conventional subgroups, across clinical status at presentation, irrespective of whether or not a patient underwent a revascularisation procedure
    • the addition of clopidogrel "significantly increased the rate of major bleeding (i.e. substantially disabling bleeding, intraocular bleeding leading to loss of vision, or bleeding necessitating transfusion of at least 2 units of blood) by 1% (from 2.7% to 3.7%), with the rate being higher both during the 30 days after randomisation (2% vs. 1.5%) and from 30 days after randomisation until the end of the trial (1.7% vs. 1.1%). Such treatment also increased the absolute rate of minor bleeding complications from 2.4% to 5.1% (1)"
    • for ever 100 patients in this higher-risk subgroup treated with conventional therapy, the addition of clopidogrel for around 9 months prevents 2 additional cardiovasclar deaths, or non-fatal MIs or strokes, but also causes 1 addtional patient to have a major bleed (1)
    • clopidogrel and percutaneous coronary intervention (PCI) - patients who underwent PCI and had been randomised to receive clopidogrel plus aspirin (compared with those on placebo plus aspirin) had an absolute reduction in the rate of cardiovascular death, MI or urgent revascularisation of 1.9% (4.5% vs. 6.4%, relative risk 0.70, 95% CI 0.50-0.97) in the 30-day period following PCI. Note however that more than 80% in each group undergoing PCI received open label treatment wth either ticlodipine or clopidogrel for a median of 30 days after PCI and therefore the results suggest the benefit observed in the 30-day perioda after PCI required treatment with clopidogrel prior to the procedure. It is unclear how clopidogrel compares with glycoprotein IIb/IIIa inhibitors

The Drugs and Therapeutics Bulletin (1) concludes that the results of the CURE study do not provide evidence that routine use of clopidogrel in addition to conventional therapy including aspirin is warranted in patients with acute coronary syndrome without ST elevation.

Reference:

1. Drugs and Therapeutics Bulletin (2002), 40 (6), 41-42.
2. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-elevation. NEJM 2001; 345;494-502.
3. Mehta SR et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-33.