Table 1

Landmark randomised controlled trials evaluating antiplatelet therapy in secondary stroke prevention

StudyStudy populationTrial designMean follow-upOutcomes
19 435 patients with AIS within 48 hours of symptom onset in 36 countriesRandomised to aspirin 300 mg daily, subcutaneous heparin, both or neither for up to 14 days.6 monthsRate 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.
21 106 patients with AIS were treated within 48 hours of symptom onset in ChinaAspirin 160 mg vs placebo for up to 4 weeks4 weeksMortality (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.
2500 patients with recent ischaemic stroke or TIA in EuropeDipyridamole 75 mg plus aspirin 325 mg or placebo three times daily2 yearsStroke 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 EuropeAspirin 25 mg two times daily, dipyridamole 200 mg two times daily, dipyridamole/aspirin or placebo2 yearsRelative stroke risk reduction compared with placebo: aspirin 18% (p=0.013), dipyridamole 16% (p=0.039), combination 37% (p Embedded Image 0.001)
ESPRIT (2006)17 2739 patients with TIA/minor stroke within 6 monthsAspirin 30–325 mg daily plus dipyridamole 200 mg two times daily vs aspirin3.5 yearsThe 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 yearsFirst recurrence of stroke (aspirin/dipyridamole vs clopidogrel): 9.0% vs 8.8%; p=NS.
Risk of major haemorrhage: 4.1% vs 3.6%,
1095 with ischaemic stroke within 1–6 months in JapanCilostazol 100 mg two times daily vs placebo1.5 yearsIschaemic 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 JapanCilostazol 100 mg two times daily vs aspirin 81 mg29 monthsRecurrence of cerebral infarction (cilostazol vs aspirin): 2.76% vs 3.71%, p=0.0357.
Haemorrhage: 0.77% vs 1.78; p=0.0004. (2019)21 1879 patients with recent ischaemic stroke and either at least 50% stenosis or more than two vascular risk factorsAspirin 81 mg or clopidogrel 75 mg and cilostazol 100 mg two times daily vs aspirin or clopidogrel1.4 yearsAnnual 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 infarctionClopidogrel 75 mg vs aspirin 325 mg daily1.9 yearsAnnual 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 hoursTicagrelor 90 mg two times daily vs aspirin 100 mg daily4 monthsRate 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.