Table 2

Randomised controlled trials evaluating dual-antiplatelet therapy (DAPT) in secondary stroke prevention

Study	Study population	Trial design	Mean follow-up	Outcomes
MATCH (2004)29	7599 patients with ischaemic stroke or TIA within 3 months	Aspirin 75 mg daily plus clopidogrel 75 mg daily or placebo plus clopidogrel 75 mg daily	18 months	Rate of primary endpoints (aspirin plus clopidogrel vs clopidogrel): 15.7% vs 16.7%, p=0.244. Rate of life-threatening bleeding: 2.6% vs 1.3%, p<0.0001
CHARISMA (2006)30	15 603 patients with cerebrovascular disease or multiple risk factors	Aspirin 75–162 mg daily plus clopidogrel 75 mg daily or aspirin 75–162 mg daily plus placebo	2.3 years	Rate of stroke, myocardial infarction or death Aspirin plus clopidogrel vs aspirin): 6.8% vs 7.3%, p=0.22 Rate of stroke 1.9% vs 2.4%, p=0.03 Rate of moderate bleeding: 2.1% vs 1.3, p<0.001
SPS3 (2012)31	3020 patients with lacunar infarcts within 180 days (n=3020)	Aspirin 325 mg daily plus clopidogrel 75 mg daily or aspirin 325 mg daily plus placebo	3.4 years	Rate of primary outcome of ischaemic or haemorrhagic stroke: 2.5% (dual) vs 2.7% (aspirin), HR 0.92, 95% CI 0.72 to 1.16, p=0.48
CHANCE (2013)32	5170 patients with minor ischaemic stroke or high-risk TIA within 24 hours of symptom onset in China.	Clopidogrel 300 mg on day 1 followed by 75 mg daily for 90 days, plus aspirin 75 mg daily for 21 days or placebo plus aspirin 75 mg daily for 90 days.	90 days	Ischaemic or haemorrhagic stroke (Clopidogrel plus aspirin vs aspirin): 8.2% vs 11.7%; HR 0.68, 95% CI 0.57 to 0.81, p 0.001. Severe or moderate bleeding: 0.3% vs 0.3%.
POINT (2018)34	4881 patients with minor ischaemic stroke or TIA within 12 hours	Clopidogrel 600 mg loading followed by 75 mg daily for 90 days plus aspirin 50–325 mg daily or placebo plus aspirin daily for 90 days	90 days	Primary outcome of recurrent stroke, death, myocardial infarction (Clopidogrel plus aspirin vs aspirin): 5.0% (dual) vs 6.5% (aspirin), p=0.02 Risks of major haemorrhage: 0.9% (dual) vs 0.4% (aspirin), p=0.02
THALES (2020)35	11 016 patients with mild-to-moderate acute non-cardioembolic ischaemic stroke, with an NIHSS score ≤5 or TIA within 24 hours after symptoms onset	Ticagrelor 180 mg loading dose followed by 90 mg two times daily plus aspirin 300–325 mg on day 1 followed by 75–100 mg daily or matching placebo plus aspirin.	30 days	Primary outcome of stroke or death (Ticagrelor plus aspirin vs aspirin): 5.5% vs 6.6%, p=0.02. Ischaemic stroke: 5.0% vs 6.3%, p=0.004. Incidence of disability: no difference Severe bleeding: 0.5% vs 0.1%, p=0.001.
SAMMPRIS (2011)38 39	451 patients with stroke within 30 days due to 70%–99% stenosis of intracranial artery	Aspirin 325 mg daily plus clopidogrel 75 mg daily or stenting plus aspirin and clopidogrel	90 days	Rate of stroke or death within 30 days (DAPT vs stenting plus DAPT): 5.8% vs 14.7%; p=0.002. Ischaemic stroke or death at year 3: 14.9% vs 23.9%, p=0.0193.
CHANCE-2 (2021)40	6412 patients with a minor ischaemic stroke or TIA and CYP2C19 loss-of-function alleles within 24 hours of symptom onset.	Ticagrelor 180 mg on day 1 followed by 90 mg two times daily or Clopidogrel 300 mg on day 1 followed by 75 mg daily. Both groups received aspirin 75 mg daily for 21 days.	90 days	New stroke (Ticagrelor plus aspirin vs clopidogrel plus aspirin): 6.0% vs 7.6%; HR 0.77, 95% CI 0.64 to 0.94, p=0.008. Severe or moderate bleeding: 0.3% vs 0.3%.
TARDIS (2018)41	3096 patients with ischaemic stroke or TIA within 48 hours after symptom onset	Aspirin (300 mg load, 75 mg daily)+clopidogrel (300 mg load, 75 mg daily)+dipyridamole 200 mg two times daily vs either clopidogrel alone or combined aspirin and dipyridamole).	90 days	The incidence of recurrent stroke or TIA (Triple therapy vs clopidogrel or Aggrenox): 6% vs 7%; adjusted OR 0.90, 95% CI 0.67 to 1.20, p=0.47. Severe bleeding: 3% vs 1%; adjusted OR 2.54, 95% CI 2.05 to 3.16, p<0·0001.

CHANCE-2, Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events; CHARISMA, Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation, Management and Avoidance; MATCH, Management of Atherosclerosis with Clopidogrel in High-Risk Patients; NIHSS, National Institutes of Health Stroke Scale; POINT, Platelet-Oriented Inhibition in New TIA; SAMMPRIS, Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis; THALES, Transient Ischaemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke; TIA, transient ischaemic attack; TRADIS, Therapy with Dipyridamole in Patients with Acute Cerebral Ischaemia.