Low-Dose Ticagrelor DAPT
Low-dose ticagrelor combined with aspirin for preventing early neurological deterioration in patients with high-risk non-disabling ischemic cerebrovascular events: a multicenter, prospective, randomized, open-label, clinical trial
Clinical Question
In patients with high-risk non-disabling ischemic cerebrovascular events (HR-NICE) presenting within 24 hours, does low-dose ticagrelor (60 mg BID) plus aspirin reduce early neurological deterioration compared with clopidogrel plus aspirin, without increasing bleeding?
Study Overview
Objective
To determine whether low-dose ticagrelor (60 mg twice daily) plus aspirin is superior to clopidogrel plus aspirin for preventing early neurological deterioration (END) within 7 days in patients with high-risk non-disabling ischemic cerebrovascular events (HR-NICE), without increasing bleeding risk.
Study Summary
- END within 7 days occurred in 10.8% (TA) vs 22.2% (LA); RR 0.55 (95% CI 0.33-0.92; p=0.023)
- Excellent functional outcome (mRS 0-1) at 90 days: 92.8% (TA) vs 80.8% (LA); RR 1.13 (95% CI 1.05-1.23; p=0.002)
- Any bleeding: 6.0% (TA) vs 4.2% (LA); RR 1.32 (95% CI 0.51-3.43; p=0.563), all mild — no increased bleeding risk
Intervention
Low-dose ticagrelor 60 mg twice daily plus aspirin vs clopidogrel plus aspirin, initiated within 24 hours of onset in HR-NICE patients.
Patients per Arm
167 per arm (total 334)
Bottom Line
Among patients with HR-NICE treated within 24 hours of onset, low-dose ticagrelor (60 mg BID) plus aspirin significantly reduced early neurological deterioration within 7 days and improved 90-day excellent functional outcome versus clopidogrel plus aspirin, without increasing bleeding risk. This regimen offers a viable alternative DAPT strategy where CYP2C19 rapid genotyping is unavailable.
Major Points
- Low-dose ticagrelor 60 mg BID + aspirin roughly halved the incidence of END within 7 days compared with clopidogrel + aspirin (10.8% vs 22.2%; RR 0.55, 95% CI 0.33-0.92; p=0.023).
- Excellent functional outcome (mRS 0-1) at 90 days was significantly higher with low-dose ticagrelor + aspirin (92.8% vs 80.8%; RR 1.13, 95% CI 1.05-1.23; p=0.002).
- Major ischemic vascular events within 90 days were numerically fewer but not statistically different (6.6% vs 10.8%; RR 0.54, 95% CI 0.26-1.09; p=0.085).
- Any bleeding events were similar between groups (6.0% vs 4.2%; RR 1.32, 95% CI 0.51-3.43; p=0.563) and all were mild; serious adverse events were also similar.
- The findings support low-dose ticagrelor + aspirin as an alternative DAPT strategy for END prevention, particularly where rapid CYP2C19 genotyping is unavailable.
Design
Study Type: Multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial
Randomization: 1
Blinding: Open-label with blinded endpoint assessment (PROBE design)
Allocation: 1:1
Enrollment Period: not reported
Follow-up Duration: 90 days
Countries: China
Sample Size: 334
Analyzed: 334
Analysis: Intention-to-treat
Power Calculation: not reported
Registration: ChiCTR2300068509 (registered February 21, 2023)
Inclusion Criteria
- High-risk non-disabling ischemic cerebrovascular events (HR-NICE)
- Enrollment within 24 hours of symptom onset
Arms
| Field | TA group (Low-dose ticagrelor + aspirin) | Control |
|---|---|---|
| N | 167 | 167 |
| Intervention | Low-dose ticagrelor 60 mg twice daily plus aspirin | Clopidogrel plus aspirin |
| Duration | not reported | not reported |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Early neurological deterioration (END) within 7 days, defined as a ≥2-point increase in NIHSS total score or ≥1-point increase in NIHSS motor score compared with baseline | Primary | 22.2% (37/167) — LA group | 10.8% (18/167) — TA group | 0.55 | 0.023 |
| Excellent functional outcome (modified Rankin Scale [mRS] 0-1) at 90 days | Secondary | 80.8% (LA) | 92.8% (TA) | RR 1.13 | 0.002 |
| Major ischemic vascular events within 90 days | Secondary | 10.8% (LA) | 6.6% (TA) | RR 0.54 | 0.085 |
| Any bleeding events (all mild) | Safety | 4.2% (7/167) — LA | 6.0% (10/167) — TA | RR 1.32 | 0.563 |
| Adverse events | Safety | 10.2% (LA) | 12.6% (TA) | 0.467 | |
| Serious adverse events | Safety | 1.8% (LA) | 0.6% (TA) | 0.339 | |
| Any bleeding (TA) | Adverse | 6.0% (10/167) | |||
| Any bleeding (LA) | Adverse | 4.2% (7/167) | |||
| Bleeding severity | Adverse | All bleeding events were mild | |||
| Adverse events (TA) | Adverse | 12.6% | |||
| Adverse events (LA) | Adverse | 10.2% | |||
| Serious adverse events (TA) | Adverse | 0.6% | |||
| Serious adverse events (LA) | Adverse | 1.8% | |||
Subgroup Analysis
not reported
Criticisms
- Open-label design (blinded endpoint assessment mitigates but does not eliminate ascertainment bias).
- Conducted entirely in China; generalizability to non-Chinese populations with different CYP2C19 allele frequencies is uncertain.
- Modest sample size (n=334); 90-day major ischemic vascular event reduction did not reach statistical significance (p=0.085), possibly reflecting limited power.
- Enrollment period, number of participating centers, and formal power calculation not reported in the available text.
- Baseline characteristics (age, sex distribution, stroke etiology) not detailed in the available text.
- Duration of antiplatelet therapy in each arm not specified in the available text.
Funding
Natural Science Foundation of Xizang Autonomous Region (XZ2024ZR-ZY107(Z)) and Dalian Medical Science Research Program (2023DF016)
Based on: Low-Dose Ticagrelor DAPT (Journal of Neurology, 2026)
Authors: Liu J, Cao H, Wang M, ..., Ji X
Citation: Liu J, Cao H, Wang M, et al. Low-dose ticagrelor combined with aspirin for preventing early neurological deterioration in patients with high-risk non-disabling ischemic cerebrovascular events: a multicenter, prospective, randomized, open-label, clinical trial. J Neurol. 2026;273:568.
Content summarized and formatted by NeuroTrials.ai.