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Evidence summaries

Thienopyridine Derivatives (Ticlopidine, Clopidogrel) Versus Aspirin or Aspirin-Dipyridamole for Preventing Serious Vascular Events in High Risk Patients

Ticlopidine and clopidogrel are slightly but significantly more effective than aspirin in preventing serious vascular events in high-risk individuals (and specifically in TIA/stroke patients). Clopidogrel and aspirin plus dipyridamole are as effective in reducing the risk of recurrent stroke. The risk of major haemorrhagic events, including intracranial haemorrhage, is lower with clopidogrel. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 10 studies with a total of 26 865 subjects. Aspirin was compared with ticlopidine in 9 trials (7 633 patients) and clopidogrel in one trial (19 185 patients). Allocation to a thienopyridine was associated with a modest, yet statistically significant, reduction in the odds of a serious vascular event (11.6% vs 12.5%, OR 0.92, 95% CI 0.85 to 0.99) corresponding to the avoidance of 10 (95% CI 0 to 20) serious vascular events per 1 000 patients treated for about 2 years. There was also a statistically non-significant reduction in stroke (5.8 vs 6.3%, OR 0.91, 95% CI 0.82 to 1.01; 5 (95% CI 0 to 10) strokes avoided per 1 000 patients treated for two years. Compared with aspirin, thienopyridines produced a significant reduction in the odds of gastrointestinal haemorrhage and other upper gastrointestinal upset, but a significant increase in the odds of skin rash and diarrhoea. The odds of skin rash were greater for ticlopidine than for clopidogrel. Allocation to ticlopidine, but not of clopidogrel, was associated with a significant increase in the odds of neutropenia (2.3% vs 0.8%). In patients with TIA/ischaemic stroke, the results were similar to those for all patients combined.

A randomized, placebo-controlled study 2 involving 20 332 patients with a recent stroke compared 25 mg of aspirin plus 200 mg of extended-release dipyridamole (ASA-ERDP) twice daily vs. 75 mg of clopidogrel daily. The mean follow-up was 2.5 years. The primary outcome, first recurrence of stroke occurred in 9.0% of the patients receiving ASA-ERDP and in 8.8% of patients receiving clopidogrel (HR 1.01, 95% CI 0.92 to 1.11). The secondary outcome, composite of stroke, myocardial infarction or death from vascular causes, occurred in 13.1% of the patients in each group (HR for ASA-ERDP 0.99, 95% CI 0.92 to 1.07). There were more major haemorrhagic events in the ASA-ERDP group than in the clopidogrel group (4.1% vs. 3.6%, HR 1.15, 95% CI 1.00 to 1.32), including intracranial haemorrhage (HR 1.42, 95% CI 1.11 to 1.83). The net risk of recurrent stroke or major haemorrhagic event was similar in the two groups (11.7% in the ASA-ERDP group vs. 11.4% in the clopidogrel group, HR1.03; 95% CI 0.95 to 1.11). The trial showed similar rates of recurrent stroke with ASA-ERDP and clopidogrel.

    References

    • Sudlow CL, Mason G, Maurice JB, Wedderburn CJ, Hankey GJ. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2009;(4):CD001246. [PubMed].
    • Sacco RL, Diener HC, Yusuf S, et al; PRoFESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008 Sep 18;359(12):1238-51. [PubMed]

Primary/Secondary Keywords