Feedback from David K. Cundiff, MD
Mrs Hazel Fraser
Review Group Co-ordinator
Division of Clinical Neurosciences
EH4 2XU
Sent 6/25/07 Re: P Sandercock, O Mielke, M Liu, C Counsell. Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD000248. DOI: 10.1002/14651858.CD000248 (Stroke)
Dear Mrs. Fraser,
Please consider the criticisms below of the Cochrane review of anticoagulant treatment for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack.
I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.
Thank you.
Best wishes,
David K. Cundiff, MD
This review, published in 2003, found no evidence for a net benefit of anticoagulants for secondary prevention of symptomatic cranial artery stenosis. Yet the implications for research included the point, “Since antiplatelet therapy has now been shown to be effective in secondary prevention, it is no longer ethical to include an untreated control group. The questions that now need to be answered are:
a) whether anticoagulant therapy alone is better than antiplatelet therapy alone, which is being addressed by three trials (ESPRIT, WASID and AVASIS)….”
In 2005, the Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis (WASID) trial was terminated early because of the high incidence of death in the warfarin group (4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group; hazard ratio for aspirin relative to warfarin, 0.46; 95 percent confidence interval, 0.23 to 0.90; P=0.02).1 The authors concluded, “Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.” This Cochrane Review should be updated to indicate that vitamin k inhibitors should be contraindicated in acute ischemic stroke. No further anticoagulant drug research is warranted in this patient group.
The next point in the implications for research was “b) whether anticoagulation adds worthwhile benefit to antiplatelet therapy (without an unacceptable increase in the risk of haemorrhage)….”
Further research involving adding anticoagulants to aspirin for this indication would be unethical because the lack of overall benefit of anticoagulants in multiple trials and the demonstrated increase in bleeding risk.
1. Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis. N Engl J Med. March 31, 2005;352(13):1305-1316.