Table 1
Landmark randomised controlled trials evaluating antiplatelet therapy in secondary stroke prevention
| Study | Study population | Trial design | Mean follow-up | Outcomes |
| IST (1997)12 | 19 435 patients with AIS within 48 hours of symptom onset in 36 countries | Randomised to aspirin 300 mg daily, subcutaneous heparin, both or neither for up to 14 days. | 6 months | Rate of dependence at 6 months (aspirin vs no aspirin): 62.2% vs 63.5%, p=0.07. Ischaemic stroke at 14 days (aspirin vs no aspirin): 2.8% vs 3.9%, p<0.001. |
| CAST (1997)13 | 21 106 patients with AIS were treated within 48 hours of symptom onset in China | Aspirin 160 mg vs placebo for up to 4 weeks | 4 weeks | Mortality (aspirin vs placebo): 3.3% vs 3.9%, p=0.04. Recurrent ischaemic stroke (aspirin vs placebo): 1.6% vs 2.1%, p=0.01. |
| ESPS (1987)15 | 2500 patients with recent ischaemic stroke or TIA in Europe | Dipyridamole 75 mg plus aspirin 325 mg or placebo three times daily | 2 years | Stroke and death (dipyridamole/aspirin vs placebo): 33% relative risk reduction (p<0.01). |
| ESPS-2 (1996)16 | 6600 patients with prior stroke or TIA within 3 months in Europe | Aspirin 25 mg two times daily, dipyridamole 200 mg two times daily, dipyridamole/aspirin or placebo | 2 years | Relative stroke risk reduction compared with placebo: aspirin 18% (p=0.013), dipyridamole 16% (p=0.039), combination 37% (p  0.001) |
| ESPRIT (2006)17 | 2739 patients with TIA/minor stroke within 6 months | Aspirin 30–325 mg daily plus dipyridamole 200 mg two times daily vs aspirin | 3.5 years | The composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction or major bleeding complication (Aspirin/dipyridamole vs aspirin): 12.7% vs 15.7%, HR: 0.80, 95% CI 0.66 to 0.98. |
| PRoFESS (2008)18 | 20 332 patients with ischaemic stroke within 90 days of randomisation and an age of 50 years or older. | Aspirin/dipyridamole (25/200 mg) two times daily vs clopidogrel 75 mg daily | 2.5 years | First recurrence of stroke (aspirin/dipyridamole vs clopidogrel): 9.0% vs 8.8%; p=NS. Risk of major haemorrhage: 4.1% vs 3.6%, p=NS. |
| CSPS (2000)19 | 1095 with ischaemic stroke within 1–6 months in Japan | Cilostazol 100 mg two times daily vs placebo | 1.5 years | Ischaemic stroke relative risk reduction (cilostazol vs placebo): 41.7% (95% CI 9.2% to 62.5%; p=0.015) |
| CSPS-2 (2010)20 | 2757 patients with a cerebral infarction within previous 26 weeks in Japan | Cilostazol 100 mg two times daily vs aspirin 81 mg | 29 months | Recurrence of cerebral infarction (cilostazol vs aspirin): 2.76% vs 3.71%, p=0.0357. Haemorrhage: 0.77% vs 1.78; p=0.0004. |
| CSPS.com (2019)21 | 1879 patients with recent ischaemic stroke and either at least 50% stenosis or more than two vascular risk factors | Aspirin 81 mg or clopidogrel 75 mg and cilostazol 100 mg two times daily vs aspirin or clopidogrel | 1.4 years | Annual rate of recurrent stroke (DAPT vs SAPT): 2.2% vs 4.5%, HR 0.49 (95% CI 0.31 to 0.76; p=0.001) |
| CAPRIE (1996)24 | 19 185 patients with either recent ischaemic stroke or myocardial infarction | Clopidogrel 75 mg vs aspirin 325 mg daily | 1.9 years | Annual rate of ischaemic stroke, myocardial infarction or cardiovascular death (Clopidogrel vs aspirin): 5.32% vs 5.83%, p=0.043. |
| SOCRATES (2016)25 | 13 199 patients with recent stroke or high-risk TIA within previous 24 hours | Ticagrelor 90 mg two times daily vs aspirin 100 mg daily | 4 months | Rate of recurrent stroke, myocardial infarction or death (Ticagrelor vs aspirin): 6.7% vs 7.5%, p=0.07. Rate of ischaemic stroke: 5.8% vs 6.7%; p=0.046. |
AIS, acute ischaemic stroke; CAPRIE, Clopidogrel vs Aspirin in Patients at Risk of Ischaemic Events; CAST, Chinese Acute Stroke Trial; CSPS, Cilostazol stroke prevention study ; DAPT, dual-antiplatelet therapy; ESPRIT, European Stroke Prevention in Reversible Ischaemia Trial; ESPS, European Stroke Prevention Study 2; IST, International Stroke Trial; NS, not significant; PRoFESS, Prevention Regimen for Effectively Avoiding Second Strokes; SAPT, single-antiplatelet therapy; SOCRATES, Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes; TIA, transient ischaemic attack.