| Methods | R: computer‐generated randomisation sequence by means of a dynamic balancing method with stratification by age, sex, and study institution using patient information obtained at registration. Randomization number was assigned to every drug pack. Patients were given treatment number identical to the numbered drug pack C: double dummy method. Parallel assignment, with placebo tablets identical to drug that patient was not assigned. The person responsible for drug allocation sealed assignment list immediately after assignment, and kept it sealed until designated point of unmasking B: all participants, study personnel, investigators, and sponsors were masked to treatment allocation | |
| Participants | 279 centres in Japan (2003 to 2006) 2757 patients Mean age: 63.5 years (20 to 80 years) Sex: 71.7% men Inclusion criteria: cerebral infarction within 26 weeks prior to enrolment and whose symptoms had remained stable, confirmed by neuroimaging, patients with no cardiac diseases that may be associated with cardiogenic cerebral embolism (mitral stenosis, prosthetic heart valve, endocarditis, myocardial infarction within 6 weeks after occurrence, ventricular aneurysm, endocardial thrombosis, mitral valve prolapse, atrial fibrillation, sick sinus syndrome, idiopathic cardiomyopathy, and patent foramen ovale), patients without asymptomatic cerebral infarction, those who had not undergone or scheduled for percutaneous transluminal angioplasty or revascularization for the treatment of cerebral infarction), without severe disturbances/impairment following cerebral infarction Exclusion criteria: patients with haemorrhage or bleeding tendency (haemophilia, capillary fragility, intracranial haemorrhage, haemorrhage in the digestive tract, haemorrhage in the urinary tract, haemoptysis, and haemorrhage in the vitreous body, pregnant, possibly pregnant, or nursing women, ischaemic heart failure, peptic ulcer, severe blood disorders, severe hepatic or renal disease, malignant neoplasm or patients who have received any therapy for malignant neoplasm within 5 years prior, history of hypersensitivity to salicylic acid formulations or ingredients of cilostazol tablets, aspirin asthma (asthma attacks induced by non‐steroidal anti‐inflammatory analgesic agents) or a history of aspirin asthma, treatment with ticlopidine hydrochloride | |
| Interventions | Cilostazol oral tablet, 100 mg twice a day and placebo of aspirin once daily versus aspirin oral tablet, 81 mg once a day and placebo of cilostazol twice a day Duration of treatment: 1 to 5 years | |
| Outcomes | Primary outcome: occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage) Secondary outcomes: first recurrence of cerebral infarction; ischaemic cerebrovascular events including cerebral infarction or transient ischaemic attack; death from any cause; and composite of completed stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage), transient ischaemic attack, angina pectoris, myocardial infarction, heart failure, or haemorrhage requiring hospital admission (excluding cerebral haemorrhage and subarachnoid haemorrhage) | |
| Notes | Of the 2757 participants enrolled and randomly allocated, 23 in the cilostazol arm and 18 in the aspirin arm did not receive treatment due to withdrawal, recurrence of cerebral infarction, or met exclusion criteria Overall, 2716 participants received study drug treatment, of which 19 were ineligible for analysis in the cilostazol arm and 25 were ineligible in the aspirin arm Of these, a further 457 participants discontinued drug in the cilostazol arm, of which 267 were due to adverse drug reactions In the aspirin arm 336 participants discontinued treatment, of which 166 were due to adverse drug reactions Eventually 2672 were included in the analysis | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | Double‐dummy method and parallel assignment |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Double blinding (participant, caregiver, investigator, sponsor) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All patients lost to follow up accounted for |
| Selective reporting (reporting bias) | Low risk | All selected patients accounted for |
| Other bias | Low risk | All outcomes addressed |
B: blinding C: control R: randomisation Rx: treatment