News: Value of CURE results questioned

The Pharmaceutical Journal Vol 267 No 7162 p251-255
25 August 2001

Value of CURE results questioned

Results of the CURE (clopidogrel in unstable angina to prevent recurrent ischaemic events) trial published last week have led to debate about the cost-effectiveness of antiplatelet therapies.

The trial results showed that the antiplatelet drug clopidogrel (Plavix) has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. (ST-segment elevations often occur in patients suffering a myocardial infarction, whereas depressions are seen in patients with unstable angina.)

Reports in the national press have indicated that use of clopidogrel with aspirin could save thousands of lives in Britain each year (The Independent, 16 August, p1, The Guardian, 16 August, p1).

Dr Brian Curwain, prescribing adviser, New Forest Primary Care Trust, told The Journal that media hype surrounding the study was entirely unjustified. The study results were based on a composite primary outcome measure of death from cardiovascular causes, non-fatal myocardial infarction (MI) or stroke. When the results for an outcome measure of only death are analysed, the results become non-significant, he said.

“The study actually demonstrates that in this group, if you treat 48 patients with clopidogrel plus aspirin, then 47 will not have their outcomes changed during the nine months after their MI.” The 48th patient would have their outcome altered as a result of receiving the drug, and would not die or suffer a non-fatal MI or stroke.

Dr Curwain pointed out that use of clopidogrel would be associated with an increased number of major bleeds, and that the cost to the National Health Service of treating 48 patients for nine months with the drug would be approximately £20,000.

“The question is, what else could we do with £20,000... If you are looking for value for money, then aspirin is the drug. Adding clopidogrel gives a very small enhanced effect by certain outcome measures, but not by preventing death.”

The CURE trial involved 12,562 patients with acute coronary syndrome who were randomised to receive either aspirin or aspirin plus clopidogrel for between three and 12 months. The primary outcome of the study — a composite of death from cardiovascular causes, non-fatal MI and stroke — occurred in 9.3 per cent of patients taking clopidrogrel and 11.4 per cent of patients taking placebo (relative risk with clopidogrel as compared with placebo, 0.80, 95 per cent confidence interval, 0.72 to 0.90, P<0.001). Dr Curwain commented that the reported relative risk reduction of 20 per cent was derived from an absolute risk reduction of about 2 per cent.

The results of the study, now published in The New England Journal of Medicine (2001;345:494), were originally presented at the 50th American College of Cardiology meeting in Florida in March (PJ, 24 March). Results of a sub-analysis of the CURE study, comparing the effects of clopidogrel and placebo in patients undergoing percutaneous coronary intervention, were published in The Lancet last week (PJ, 18 August).