Low-dose ticagrelor with aspirin halved early deterioration after minor stroke and TIA

Design

Multicentre, prospective, randomised, open-label, blinded-endpoint trial in China; intention-to-treat

Population

334 patients presenting within 24 hours of a high-risk non-disabling ischaemic cerebrovascular event

Primary outcome

Early neurological deterioration within 7 days (NIHSS rise of 2 or more points, or 1 point on the motor score)

Effect

10.8% vs 22.2%; RR 0.55 (95% CI 0.33 to 0.92, p = 0.023)

A multicentre Chinese trial randomised 334 patients presenting within 24 hours of a high-risk non-disabling ischaemic cerebrovascular event to either ticagrelor 60 mg twice daily with aspirin, or clopidogrel with aspirin. It was open-label with blinded endpoint adjudication. Early neurological deterioration within seven days — a rise of two or more NIHSS points, or one point on the motor score — occurred in 10.8% on ticagrelor against 22.2% on clopidogrel, relative risk 0.55 (95% CI 0.33 to 0.92, p = 0.023). Excellent functional outcome at 90 days, modified Rankin 0 to 1, was 92.8% against 80.8% (RR 1.13, 1.05 to 1.23). Major ischaemic vascular events at 90 days did not differ significantly, 6.6% against 10.8%. Bleeding occurred in 6.0% and 4.2%, all of it mild.

The rationale is pharmacogenetic. Clopidogrel needs CYP2C19 activation, and loss-of-function alleles are common in East and South Asian populations, so a proportion of patients on clopidogrel-based dual therapy are effectively on aspirin alone. Ticagrelor does not require that conversion, and the 60 mg dose was chosen to hold down bleeding risk. The authors position it explicitly as an option where rapid genotyping is unavailable — which describes most Indian centres outside large private hospitals.

Read the size of the trial before changing a protocol. Three hundred and thirty-four patients, an open-label design and a primary endpoint that depends on clinical scoring is a combination that inflates effects. The 90-day functional difference of twelve percentage points is larger than the mechanism plausibly delivers and larger than earlier ticagrelor trials found. Treat this as support for ticagrelor where clopidogrel resistance is suspected or genotyping is impossible, not as a reason to displace clopidogrel generally.

• Consider ticagrelor-based dual therapy where CYP2C19 genotyping is unavailable and clopidogrel non-response would go undetected.
• The dose studied was 60 mg twice daily, not the 90 mg acute coronary regimen.
• Ask about dyspnoea before starting ticagrelor and warn the patient — it is the usual reason for discontinuation.
• Dual antiplatelet therapy here is short-course for a minor event, not indefinite; set the stop date when you start.
• Deterioration was defined by NIHSS change, so serial scoring in the first week is what detects it.

The statistics, in plain English

A relative risk of 0.55 with an interval of 0.33 to 0.92 excludes no effect, but the upper bound sits close to it — the data are compatible with a reduction of only 8% as well as the two-thirds suggested by the point estimate. With 55 events in total, one or two reclassified patients would move that interval across 1.0. Open-label allocation matters more than usual here because the primary endpoint is a clinical score assessed at the bedside, and knowing the assigned drug can shade a one-point motor rating. The 90-day secondary outcome is more robust to that, but it is a secondary outcome in a trial not powered for it.

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