TREAT-CAD RCT – Aspirin or Warfarin for Cervical Arterial Dissection?

Written by Clay Smith

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Aspirin was not non-inferior to vitamin K antagonists (VKA) in reducing bad clinical and MRI outcomes at 14 days in adult patients with cervical arterial dissection (CAD).

Why does this matter?
In the past, most patients with CAD have been treated with VKAs. However, there has been a trend, after publication of CADISS, to treat them with antiplatelet agents only, which is much simpler. Of note, CADISS allowed dual antiplatelet therapy, unlike this study. Is aspirin enough to prevent stroke?

This was an open-label randomized, non-inferiority trial that enrolled 194 patients with MRI-proven CAD to receive either aspirin 300mg daily or a VKA (INR goal 2-3) for 90 days to determine whether aspirin was non-inferior to VKAs in preventing subsequent bad clinical and imaging outcomes. The primary outcome was a composite of, “clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population.” The primary outcome occurred in 21/91 (23%) in the aspirin group and in 12/82 (15%) in the VKA group, an 8% absolute difference (95%CI -4% to 21%). Since this was a non-inferiority trial, they determined before the study began that the highest upper 95%CI number they would accept as the “non-inferiority margin” would be 12%. To me, 12% seems quite high, and this would have been an issue had they found non-inferiority, but the highest upper 95%CI was 21%, which means aspirin was not non-inferior. When looking purely at subsequent ischemic events, there were 7 strokes (8%) in the aspirin group and none in the VKA group. The groups seemed to be similar in terms of safety, though there were numerically more minor adverse events in the VKA group (n=26) than the aspirin group (n=19). MRI outcomes occurred 4-times more often than clinical outcomes, as the authors thought would happen. It is not clear the significance of new ischemia on MRI without clinical signs; but, generally, having strokes and losing neurons – whether silent or not – is not a good thing. At 3 months, 77% in each group had excellent functional outcomes (mRS 0-1). Based on all these results, we might be tempted to say aspirin is inferior to VKAs, but we can’t say that with a non-inferiority trial design, as it was not powered to detect superiority of one treatment over another. However, I know which treatment I would want. I would choose a VKA (or, these days, a direct oral anticoagulant) over aspirin alone for CAD personally and will plan to recommend this for my patients.

Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial. Lancet Neurol. 2021 May;20(5):341-350. doi: 10.1016/S1474-4422(21)00044-2. Epub 2021 Mar 23.

What are your thoughts?

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