Conclusion
Discussant: Verheugt, F.W.A., Nijmegen, Netherlands
Three major trials have shown, that oral anticoagulation (target INR 2-3) on top of aspirin is effective in reducing cardiovascular death, reinfarction and stroke after myocardial infarction in comparison to aspirin alone1.
In other areas of atherothrombosis this combination has not been evaluated. In the WAVE trial over 2,100 patients with peripheral vascular disease were randomized to the combination oral anticoagulation (target INR 2-3, achieved INR 2.2) plus aspirin, or to aspirin alone and followed for nearly 3 years.
No benefit on cardiovascular death, myocardial infarction or stroke was observed, but there was a 3.5 times increase in severe bleeding complications including cerebral haemorrhage. Life-threatening bleeding was seen in 4.0% on the combination therapy versus 1.2% with aspirin alone (p < 0.001).
Explanations for failure to achieve benefit may be play of chance or the low baseline-risk of the patients compared to those in the large post-MI trials.
Thus, so far addition of warfarin to aspirin in patients with peripheral vascular disease does not reduce the incidence of major ischemic events, but increase severe bleeding. Alternative therapies to aspirin alone may be clopidogrel alone as found in the large CAPRIE trial2, but this trial included a mix of coronary, cerebrovascular and peripheral vascular disease patients.
Long-term addition of clopidogrel to aspirin is not effective either. Finally, a direct comparison of aspirin alone against oral anticoagulation alone in peripheral vascular surgery did not show a benefit of oral anticoagulation alone, but increased the bleeding risk4. Possibly, future antiplatelet agents and/or novel anticoagulants may protect patients with peripheral vascular disease on aspirin better
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References
1. Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J. 2006;27:519-526
2. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-1339
3. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-1717.
4. Dutch Bypass Oral Anticoagulation or Aspirin (BOA) Study Group. Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral anticoagulants or Aspirin study): a randomised trial. Lancet 2000;355:346-351
