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.