Cardiovascular

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.

Liu J, Cao H, et al. • Journal of neurology • 2026

PubMed 42704480 DOI 10.1007/s00415-026-14094-4

TL;DR

Low-dose ticagrelor (60 mg twice daily) plus aspirin significantly decreased the incidence of early neurological deterioration within 7 days and improved neurological functional outcomes at 90 days compared with clopidogrel plus aspirin, without increasing the risk of bleeding, in patients with high-risk non-disabling ischemic cerebrovascular events.

Key Findings

Results

Low-dose ticagrelor plus aspirin significantly reduced early neurological deterioration within 7 days compared to clopidogrel plus aspirin.

END occurred in 10.8% (18/167) of the TA group versus 22.2% (37/167) of the LA group.
Relative risk 0.55 (95% CI, 0.33–0.92; p=0.023).
END was defined as a ≥2-point NIHSS score increase or NIHSS motor score ≥1-point increase compared with baseline.
The trial enrolled 334 patients randomized 1:1, analyzed by intention-to-treat.

Results

Patients receiving low-dose ticagrelor plus aspirin had significantly better excellent functional outcomes at 90 days compared to the clopidogrel plus aspirin group.

Excellent functional outcome (mRS score 0–1) at 90 days was achieved in 92.8% of TA group patients versus 80.8% of LA group patients.
Relative risk 1.13 (95% CI, 1.05–1.23; p=0.002).
This represents a 12-percentage-point absolute difference in excellent functional outcomes between groups.

Results

There was no statistically significant difference between groups in major ischemic vascular events within 90 days.

Ischemic vascular events occurred in 6.6% of the TA group versus 10.8% of the LA group.
Relative risk 0.54 (95% CI, 0.26–1.09; p=0.085).
The difference did not reach statistical significance despite a numerically lower rate in the ticagrelor group.

Results

Bleeding risk did not significantly differ between low-dose ticagrelor plus aspirin and clopidogrel plus aspirin.

Any bleeding events occurred in 6.0% (10/167) of the TA group and 4.2% (7/167) of the LA group.
Relative risk 1.32 (95% CI, 0.51–3.43; p=0.563).
All bleeding events were described as mild in both groups.
No significant differences were found in adverse events (12.6% vs. 10.2%, p=0.467) or serious adverse events (0.6% vs. 1.8%, p=0.339).

Background

The study was designed to address limitations of clopidogrel-based therapy related to CYP2C19 gene polymorphism in HR-NICE patients.

Clopidogrel-based dual antiplatelet therapy is described as 'substantially limited by the CYP2C19 gene polymorphism.'
The trial was conducted in China, where CYP2C19 loss-of-function variants are prevalent.
The authors propose this regimen as a strategy for institutions 'lacking rapid genotyping facilities.'
Patients were enrolled within 24 hours of symptom onset and followed for 90 days.

Methods

The trial was a multicenter, prospective, randomized, open-label, blinded-endpoint design enrolling 334 patients with HR-NICE in China.

Patients were randomized 1:1 to low-dose ticagrelor (60 mg twice daily) plus aspirin or clopidogrel plus aspirin.
Enrollment required presentation within 24 hours of onset.
Intention-to-treat analysis was the primary analytical approach.
The trial was registered at ChiCTR2300068509, registered February 21, 2023.

What This Means

This research suggests that using a lower-than-standard dose of ticagrelor (60 mg twice daily) combined with aspirin is more effective than the standard combination of clopidogrel and aspirin at preventing early worsening of stroke symptoms in patients who have experienced a high-risk minor stroke or TIA (transient ischemic attack). In the study of 334 Chinese patients treated within 24 hours of symptom onset, only about 11% of those receiving low-dose ticagrelor plus aspirin experienced early neurological deterioration within 7 days, compared to about 22% of those receiving clopidogrel plus aspirin. Additionally, nearly 93% of patients in the ticagrelor group had excellent functional recovery at 90 days, compared to about 81% in the clopidogrel group. Importantly, this benefit came without a meaningful increase in bleeding risk. All bleeding events in both groups were mild, and the rates of serious adverse events were similarly low and comparable between groups. This is notable because ticagrelor at its standard dose (90 mg twice daily) carries a higher bleeding risk, suggesting that the lower 60 mg dose may offer a favorable balance between effectiveness and safety. This research is particularly relevant because a common genetic variation (in the CYP2C19 gene) reduces how well many people — especially those of East Asian descent — metabolize clopidogrel, making it less effective for them. Since genetic testing is not always quickly available in clinical settings, low-dose ticagrelor plus aspirin could serve as a practical alternative treatment strategy for preventing stroke worsening, regardless of a patient's genetic profile.

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Citation

Liu J, Cao H, Wang M, Jiao Y, Zhou R, Tang Y, et al.. (2026). 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.. Journal of neurology. https://doi.org/10.1007/s00415-026-14094-4

Key Findings

What This Means

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