Key result
Triple antiplatelet therapy shows no benefit over guideline therapy for 90-day stroke recurrence and severity.
Why the study?
Dual antiplatelet therapy reduces early recurrence after non-cardioembolic stroke or TIA, but the effect of triple antiplatelet therapy with symptomatic carotid stenosis was unknown.
Does triple antiplatelet therapy reduce stroke recurrence and its severity in patients with non-cardioembolic ischaemic stroke or TIA compared to guideline therapy?
RCT (n=3,096)
Does triple antiplatelet therapy reduce stroke recurrence and its severity in patients with non-cardioembolic ischaemic stroke or TIA compared to guideline therapy?
In patients with recent non-cardioembolic stroke or TIA, triple antiplatelet therapy did not improve stroke recurrence or severity at 90 days compared to guideline therapy, even in those with severe symptomatic carotid stenosis.
Does not support severity-based intensification of antiplatelet therapy; leaves open dedicated trials in high-grade symptomatic stenosis.[[1]](https://anrs-neurologie.ro/wp-content/uploads/2023/10/ESO-stenoze-artere-intracraniene-2022.pdf)[[2]](https://eso-stroke.org/wp-content/uploads/ESO-GL-ICAD.
Background and aims Dual antiplatelet therapy reduces early recurrence in patients with acute non-cardioembolic minor ischaemic stroke or transient ischaemic attack (TIA). The effect of triple antiplatelet therapy in the presence of symptomatic carotid stenosis is unknown. We sought to assess the effect of triple vs. guideline antiplatelet therapy using data from the Triple Antiplatelet for Reducing Dependency after Ischaemic Stroke (TARDIS) trial. Methods TARDIS randomised 3096 patients within 48 hours of non-cardioembolic ischaemic stroke or TIA to triple antiplatelet therapy (aspirin-clopidogrel-dipyridamole) or guideline therapy (clopidogrel, or aspirin-dipyridamole) for 30 days. The primary outcome was stroke recurrence and its severity using the modified Rankin Scale (mRS) at day 90. Symptomatic ipsilateral carotid stenosis was split: <30%; 30-50%; 50-70%; >70%. Data are odds ratios (OR) with 95% confidence intervals (CI) adjusted for baseline prognostic factors. Results 2839/3096 (91.7%) participants had carotid imaging. Compared with participants with <30%, >70% symptomatic stenosis participants were older, more were male, current smokers, had hypertension, presented with ischaemic stroke versus TIA, a higher NIHSS, and underwent thrombolysis. At 90 days, stroke recurrence and its severity did not differ between participants with >70% symptomatic stenosis versus those with <30% stenosis: OR 1.28, 95% CI 0.69-2.38, p=0.43. Randomisation to triple vs. guideline antiplatelet therapy did not influence the primary outcome in participants with >70% symptomatic stenosis (OR 2.32, 95% CI 0.33-16.28, p=0.40) or other symptomatic stenosis groups. Conclusions Severe symptomatic carotid stenosis was not associated with stroke recurrence and its severity; triple vs. guideline antiplatelet therapy did not effect this. Conflict of interest JP Appleton: nothing to disclose; K Krishnan: nothing to disclose; LJ Woodhouse: nothing to disclose; TJ England: nothing to disclose; N Sprigg: nothing to disclose; PM Bath: nothing to disclose
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Appleton et al. (2026) conducted an RCT in non-cardioembolic ischaemic stroke or TIA (n=3,096). triple antiplatelet therapy (aspirin-clopidogrel-dipyridamole) vs. guideline therapy (clopidogrel, or aspirin-dipyridamole) was evaluated on stroke recurrence and its severity using the modified Rankin Scale (mRS) at day 90 (OR 2.32, 95% CI 0.33-16.28, p=0.40). Triple antiplatelet therapy did not improve 90-day stroke recurrence and severity versus guideline therapy in patients with >70% symptomatic carotid stenosis (OR 2.32; 95% CI 0.33-16.28; p=0.40).
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