Wern Yew Ding, MBChB

Li ZX, Xiong Y, Gu HQ, Fisher M, Xian Y, Johnston SC, Wang YJ. P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack. Stroke. 2021;52:2250–2257.

Patients with ischemic stroke or transient ischaemic attack (TIA) are at risk of further events. Previously, these patients were treated with single antiplatelet therapy. However, contemporary guidelines recommend that dual-antiplatelet therapy (DAPT) may be considered in the acute phase: the duration of treatment depending on stroke severity. Several studies have investigated the use of different DAPT regimens in patients with minor stroke or high-risk TIA.

In this study by Li and colleagues, the authors undertook a systematic review and meta-analysis of 4 randomized controlled trials that included a total of 21493 patients with acute minor stroke (NIHSS score ≤3/≤5) or high-risk TIA (ABCD2 ≥4/≥6) who were randomized to receive either DAPT or aspirin alone within 24 hours of symptom onset. Three of the 4 studies used clopidogrel while the remaining study investigated the use of ticagrelor. The authors reported that DAPT reduced the risk of stroke recurrence by 24%. However, there was no statistical difference in all-cause mortality between the groups, and those on DAPT were exposed to a 2.2-fold greater risk of moderate or severe bleeding.

Overall, the findings suggest that there may be a role for DAPT in patients with acute minor stroke or high-risk TIA. However, there are several points that are worth our attention. Firstly, there was significant variation in the DAPT regimen used in different studies in terms of antithrombotic of choice (clopidogrel/ticagrelor), dosage and treatment duration (range from 21-90 days) such that the optimal antithrombotic regimen remains to be defined. Furthermore, the follow-up duration was relatively short in these studies (90 days in 3; 30 days in 1), and, therefore, more long-term data should be sought. Interestingly, though the overall results were neutral for hemorrhagic stroke and intracranial hemorrhage, there was a statistically significant increased risk of these events for DAPT with ticagrelor (THALES trial), as may have been expected with this more potent antithrombotic agent in comparison to clopidogrel. In many ways, the quest for the optimal antithrombotic therapy in patients with acute stroke resembles that in patients with acute coronary syndrome. In principle, increased antithrombotic therapy should reduce the risk of ischemia at the expense of a greater risk of major bleeding. The real question is where to draw the line in terms of stroke risk reduction vs. risk of major bleeding. Other potential regimens to explore include single antiplatelet therapy with a P2Y12 inhibitor and low-dose anticoagulation in isolation or as add-on therapy. Further studies are needed on this important topic.