Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients - PubMed (original) (raw)
Review
Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients
Cathie Lm Sudlow et al. Cochrane Database Syst Rev. 2009.
Abstract
Background: Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events, reducing the odds of such events among high vascular risk patients by about a quarter. Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective.
Objectives: To determine the effectiveness and safety of thienopyridine derivatives (ticlopidine and clopidogrel) versus aspirin for preventing serious vascular events (stroke, myocardial infarction (MI) or vascular death) in patients at high risk, and specifically in patients with a previous TIA or ischaemic stroke.
Search strategy: We searched the trials registers of the Stroke, Heart and Peripheral Vascular Diseases Cochrane Review Groups (last searched July 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2008), MEDLINE (1966 to August 2008) and EMBASE (1980 to August 2008). We also searched reference lists of relevant papers, and contacted other researchers and the pharmaceutical company Sanofi-BMS (December 2008).
Selection criteria: All unconfounded, double blind, randomised trials directly comparing a thienopyridine derivative with aspirin in high vascular risk patients.
Data collection and analysis: Two review authors independently extracted data and assessed trial quality. We sought additional data from the principal investigators of the largest trials.
Main results: We included 10 trials involving 26,865 high vascular risk patients. The trials were generally of high quality. Aspirin was compared with ticlopidine in nine trials (7633 patients) and with clopidogrel in one trial (19,185 patients). Compared with aspirin, allocation to a thienopyridine produced a modest, just statistically significant, reduction in the odds of a serious vascular event (11.6% versus 12.5%; odds ratio (OR) 0.92, 95% confidence interval (CI) 0.85 to 0.99), corresponding to the avoidance of 10 (95% CI 0 to 20) serious vascular events per 1000 patients treated for about two years. However, the wide confidence interval includes the possibility of negligible additional benefit. Compared with aspirin, thienopyridines significantly reduced gastrointestinal adverse effects. However, thienopyridines increased the odds of skin rash and diarrhoea, ticlopidine more than clopidogrel. Allocation to ticlopidine, but not clopidogrel, significantly increased the odds of neutropenia. In patients with TIA/ischaemic stroke, the results were similar to those for all patients combined.
Authors' conclusions: The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk, and possibly somewhat more so. However, the size of any additional benefit is uncertain and could be negligible. Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice. It should be used as an alternative to aspirin in patients genuinely intolerant of or allergic to aspirin.
Conflict of interest statement
Prof Graeme Hankey has received honoraria for lecturing at scientific symposia sponsored by Sanofi Aventis, Bristol Meyers Squibb, and Boehringer Ingelheim, and has received fees for consulting from Sanofi Aventis, Bristol Meyers Squibb, and Boehringer Ingelheim.
Figures
1.1. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 1 Stroke, MI or vascular death during follow up.
1.2. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 2 Stroke, MI or vascular death (thienopyridine subgroups).
1.3. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 3 Stroke (of all types) during follow up.
1.4. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 4 Ischaemic/unknown stroke during follow up.
1.5. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 5 Haemorrhagic stroke (symptomatic intracranial haemorrhage) during follow up.
1.6. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 6 Myocardial infarction (MI) during follow up.
1.7. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 7 Vascular death during follow up.
1.8. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 8 Death from any cause during follow up.
1.9. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 9 Extracranial haemorrhage during follow up.
1.10. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 10 Gastrointestinal haemorrhage during follow up.
1.11. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 11 Indigestion/nausea/vomiting during follow up.
1.12. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 12 Neutropenia during follow up.
1.13. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 13 Any neutropenia (thienopyridine subgroups).
1.14. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 14 Thrombocytopenia during follow up.
1.15. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 15 Any thrombocytopenia (thienopyridine subgroups).
1.16. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 16 Skin rash during follow up.
1.17. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 17 Any skin rash (thienopyridine subgroups).
1.18. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 18 Diarrhoea during follow up.
1.19. Analysis
Comparison 1 Thienopyridine versus aspirin in high vascular risk patients, Outcome 19 Any diarrhoea (thienopyridine subgroups).
2.1. Analysis
Comparison 2 Thienopyridine versus aspirin in patients with TIA or ischaemic stroke, Outcome 1 Stroke, MI, or vascular death during follow up.
2.2. Analysis
Comparison 2 Thienopyridine versus aspirin in patients with TIA or ischaemic stroke, Outcome 2 Ischaemic/unknown stroke during follow up.
2.3. Analysis
Comparison 2 Thienopyridine versus aspirin in patients with TIA or ischaemic stroke, Outcome 3 Stroke (of all types) during follow up.
2.4. Analysis
Comparison 2 Thienopyridine versus aspirin in patients with TIA or ischaemic stroke, Outcome 4 Haemorrhagic stroke (symptomatic intracranial haemorrhage) during follow up.
3.1. Analysis
Comparison 3 Thienopyridine versus aspirin in high vascular risk patients ‐ sensitivity analysis, Outcome 1 Serious vascular events (sensible worst case scenario).
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- Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients.
Hankey GJ, Sudlow CL, Dunbabin DW. Hankey GJ, et al. Cochrane Database Syst Rev. 2000;(2):CD001246. doi: 10.1002/14651858.CD001246. Cochrane Database Syst Rev. 2000. PMID: 10796426 Updated. Review.
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