Authors' objectives:

This review examines the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to prophylactic doses of aspirin for the secondary prevention of occlusive vascular events.

Authors' results and conclusions: Clinical effectiveness Clopidogrel: One RCT, the CAPRIE trial, was identified that investigated the use of clopidogrel for the secondary prevention of occlusive vascular events. In addition, 15 papers reporting on additional aspects of the CAPRIE trial were identified. The point estimate for the primary outcome (ischaemic stroke, myocardial infarction (MI) or vascular death) favoured clopidogrel over aspirin, but the boundaries of the confidence intervals raise the possibility that clopidogrel is not more beneficial than aspirin. In terms of the secondary outcomes reported, there was a non-significant trend in favour of clopidogrel over aspirin but the boundaries of the confidence intervals on the relative risks all crossed unity. There was no difference in the number of patients ever reporting any bleeding disorder in the clopidogrel group compared with the aspirin group. The incidences of rash and diarrhoea were statistically significantly higher in the clopidogrel group than the aspirin group. Patients in the aspirin group had a higher incidence of indigestion/nausea/vomiting than patients in the clopidogrel group. Haematological adverse events were rare in both the clopidogrel and aspirin groups. No cases of thrombotic thrombocytopenic purpura were reported in either group. MR-dipyridamole: One RCT, ESPS-2, was identified which investigated the use of MR-dipyridamole and acetylsalicylic acid (ASA)MR-dipyridamole for the secondary prevention of occlusive vascular events. In addition, four papers reporting on additional aspects of the trial were identified. Treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2 compared with treatment with aspirin. ASAMR-dipyridamole was significantly more effective than aspirin alone in patients with stroke or TIAs at reducing the outcome of stroke and marginally more effective at reducing stroke and/or death. Treatment with ASAMR-dipyridamole did not statistically significantly reduce the risk of death compared to treatment with aspirin. The number of strokes was statistically significantly reduced in the ASAMR-dipyridamole group compared with the MR-dipyridamole group. In terms of the other primary outcomes, stroke and/or death and death, the results favoured treatment with ASAMR-dipyridamole but the findings were not statistically significant. There was no difference in the number of bleeding complications between the ASAMR-dipyridamole and aspirin groups. The incidence of bleeding complications (including severe and fatal bleeds) was significantly lower in the MR-dipyridamole treatment group. More patients in the MR-dipyridamole treatment groups experienced headaches compared to patients receiving treatment with aspirin alone.

Authors' recommendations: - Clopidogrel was marginally more effective than aspirin at reducing the risk of ischaemic stroke, MI or vascular death in patients with atherosclerotic vascular disease. That is, the point estimate favoured treatment with clopidogrel but the lower boundary of the 95% confidence intervals suggests that the size of this benefit may be very small. - Treatment with clopidogrel did not statistically significantly reduce the risk of vascular death or death from any cause compared with aspirin. - There was no statistically significant difference in the number of bleeding complications experienced in the clopidogrel and aspirin groups. - Compared with aspirin alone, treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2. - MR-dipyridamole in combination with aspirin was superior to aspirin alone at reducing the risk of stroke and marginally more effective at reducing the risk of stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR-dipyridamole in combination with aspirin significantly reduced the risk of stroke. - Treatment with MR-dipyridamole in combination with aspirin did not statistically significantly reduce the risk of death compared with aspirin. - Compared with treatment with MR-dipyridamole alone, bleeding complications were statistically significantly higher in patients treated with aspirin and MR-dipyridamole in combination with aspirin. - Due to the assumptions that have to be made, no conclusions could be drawn about the relative effectiveness of MR-dipyridamole, alone or in combination with aspirin, and clopidogrel from the adjusted indirect comparison.

Authors' methods: Systematic review, Economic evaluation

Project Status: Completed

URL for project: http://www.hta.ac.uk1365

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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