The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis


Acute coronary syndrome (ACS) is a fissuring or rupturing of atheromatous plaques leading to occlusive thrombi in the arteries. Non-ST-elevation-ACS (NSTE-ACS) can be classified as unstable angina with undetectable markers but with electrocardiogram changes, or non-ST-elevation myocardial infarction (NSTEMI) where there is evidence of myocardial necrosis.

The objective of this project was to update the previous model, and formally assess the potential value and feasibility of further research to address the optimal duration of clopidogrel treatment using value of information (VOI) analysis and a Bayesian decision theoretic approach. In line with this we aimed to update the previous systematic review of the use of clopidogrel in combination with aspirin for patients with NSTE-ACS, investigating the optimal duration of treatment and effects of withdrawal from treatment.


Clopidogrel combined with aspirin reduces adverse cardiovascular events in comparison with aspirin alone in patients with NSTE-ACS, but may increase the risk of bleeding. The optimal duration of clopidogrel treatment in patients with NSTE-ACS is uncertain and requires further research. There is some evidence that a rebound effect occurs following the withdrawal of thienopyridine treatment, but its clinical significance is uncertain. The results of the updated decision model suggest that durations of clopidogrel treatment beyond 3 months do not appear to be cost-effective in patients at lower risk. However, for an average-risk patient (and in higher-risk patients), 12 months of treatment with clopidogrel appear to be cost-effective. These conclusions appeared robust to alternative assumptions related to whether the treatment effect remained constant over a 12-month period or was assumed to decline after 3 months. There is considerable variation in the costs of uncertainty surrounding the different scenarios and populations considered. The validity of these may also be less reliable in the higher-risk groups owing to changes in clinical practice. The results in the lower-risk group suggested that the upper bound of the value of a future trial was between £10.8 million and £11.9 million (and of this total, approximately 40–45% related to parameters for which a randomised design would be essential).

Conducted by: W Rogowski1, J Burch2, S Palmer3, C Craigs2, S Golder2, N Woolacott2

1. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg; 2. Centre for Reviews and Dissemination, University of York; 3. Health Economics Centre for Health Economics, University of York

Further details

Project page on HTA Programme website


Rogowski W, Burch J, Palmer S, Craigs C, Golder S, Woolacott N. The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: systematic review and value of information analysis. Health Technol Assess. 2009;13(31):1-77


Commissioned by the HTA Programme on behalf of NICE's Technology Assessment Report (TAR) process