THALES Trial: Ticagrelor + Aspirin vs Aspirin Alone After Minor Stroke or TIA
In patients with acute non-cardioembolic minor ischemic stroke or high-risk TIA presenting within 24 hours, does ticagrelor plus aspirin reduce composite stroke or death at 30 days compared with aspirin alone?
Johnston SC, et al. (NEJM 2020) · doi:10.1056/NEJMoa1916870 · 11,016 patients
Population
Included
- Age 40 years or older
- Acute non-cardioembolic ischemic stroke with NIHSS score 5 or less, or high-risk TIA (ABCD2 score 6 or higher)
- Randomization within 24 hours of symptom onset
- No indication for anticoagulation
Core qualifying event
- At least 40 years of age
- Mild-to-moderate acute noncardioembolic ischemic stroke with an NIHSS score of 5 or less
- Or a high-risk TIA with an ABCD2 score of 6 or higher, or symptomatic intracranial or extracranial arterial stenosis (>=50% narrowing that could account for the TIA)
Timing / imaging
- Randomization within 24 hours after symptom onset, or within 24 hours from last known normal for wake-up presentations
- CT or MRI before randomization to rule out hemorrhage or other conditions
- Not undergoing thrombolysis or thrombectomy
Excluded
- NIHSS score greater than 5 at baseline
- Planned carotid endarterectomy or stenting within 30 days
- Prior hemorrhagic stroke or significant bleeding risk
- Concurrent anticoagulation requirement
- Thrombolysis or thrombectomy for the index event
Planned reperfusion / antithrombotic
- Planned IV or intraarterial thrombolysis or thrombectomy within 24 hours before randomization
- Planned anticoagulation or specific antiplatelet therapy other than aspirin
- Planned carotid endarterectomy requiring discontinuation within 3 days
Cardioembolic / contraindication
- Hypersensitivity to ticagrelor or aspirin
- History of atrial fibrillation or ventricular aneurysm or suspicion of a cardioembolic cause
Bleeding risk
- A known bleeding diathesis or coagulation disorder
- A history of intracerebral hemorrhage
- Gastrointestinal bleeding within the past 6 months
- Major surgery within 30 days before randomization
Source: Johnston et al., N Engl J Med 2020· Retrieved 2026-06-09
Primary Outcome
Negligible absolute difference
Event-free at 30 Days
Study Arms
- Agent
- Ticagrelor plus aspirin
- Dose
- Ticagrelor 180 mg loading (two 90-mg tablets) as soon as possible after randomization, then 90 mg twice daily at about 12-hour intervals; aspirin 300 to 325 mg loading recommended (less if aspirin already given), then 75 to 100 mg daily
- Route
- Oral
- Frequency
- Ticagrelor twice daily; aspirin once daily
- Duration
- 30-day treatment period
- Co-interventions
- After 30 days, standard of care at investigator discretion; followed an additional 30 days
Fixed-randomization schedule, balanced blocks, about 1:1
- Agent
- Aspirin plus matching ticagrelor placebo
- Dose
- Matching ticagrelor placebo as soon as possible after randomization, then twice daily; aspirin 300 to 325 mg loading recommended (less if aspirin already given), then 75 to 100 mg daily
- Route
- Oral
- Frequency
- Placebo twice daily; aspirin once daily
- Duration
- 30-day treatment period
- Co-interventions
- After 30 days, standard of care at investigator discretion; followed an additional 30 days
Aspirin monotherapy with matching ticagrelor placebo (double-blind control)
Safety
Severe hemorrhage at 30 days (ticagrelor+ASA vs ASA alone)
0.5%
0.1%
Severe bleeding was 5x higher with ticagrelor plus aspirin versus aspirin alone (0.5% vs 0.1%, P<0.001). This disproportionate hemorrhagic risk relative to the 1.1% absolute efficacy gain is the basis for the AHA/ASA 2026 COR 3 downgrade. /* claimId: thales-severe-hemorrhage | source: Johnston NEJM 2020 Table 3 */
Trial Design
Type
- Randomized double-blind placebo-controlled trial
- International. 414 sites, 28 countries
- 1:1 allocation (ticagrelor + aspirin vs aspirin + placebo)
- 30-day treatment duration
Timeline
Enrolled 2018–2019; published NEJM 2020
N
11,016
Enrollment
11,016 patients at 414 sites in 28 countries. Enrolled 2018 to 2019. Published NEJM 2020.
ClinicalTrials.gov
NCT03354429Bedside Pearl
THALES is statistically positive (P=0.02) but the guideline verdict is COR 3 (No Benefit) because the NNT of 91 and a 5x increase in severe bleeding make it clinically inferior to clopidogrel DAPT (CHANCE NNT=28, similar safety). In practice: use aspirin plus clopidogrel for 21 days in most patients with TIA or minor stroke. Reserve ticagrelor-based DAPT for confirmed CYP2C19 poor metabolizers (CHANCE-2, COR 2b), where clopidogrel is pharmacologically inadequate.