Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial

Background Little is known about the best antiplatelet treatment immediately after ischaemic stroke or transient ischaemic attack (TIA). The EARLY trial aimed to compare outcome in patients given aspirin plus extended-release dipyridamole twice daily either within 24 h of stroke or TIA or after 7 days of aspirin monotherapy. Methods In 46 stroke units in Germany, patients aged 18 years or more who presented with symptoms of an acute ischaemic stroke that caused a measurable neurological deficit (National Institutes of Health stroke scale score <= 20) were randomly assigned to receive 25 mg aspirin plus 200 mg extended-release dipyridamole open-label twice daily or 100 mg aspirin monotherapy open-label once daily for 7 days. Patients were randomised by use of a pseudorandom number generator. All patients were then given open-label aspirin plus extended-release dipyridamole for up to 90 days. The primary endpoint was modified Rankin scale score as recorded by centralised, blinded assessment by telephone (tele-mRS) at 90 days. Vascular adverse events (non-fatal stroke, TIA, non-fatal myocardial infarction, and major bleeding complications) and mortality were assessed in a composite safety and efficacy endpoint. Patients were analysed as treated. This trial is registered, number NCT00562588. Findings Between July, 2007, and February, 2009, 543 patients were treated: 283 received early aspirin plus extended-release dipyridamole and 260 received aspirin plus extended-release dipyridamole after 7 days on aspirin. At day 90, 154 (56%) patients in the aspirin plus early extended-release dipyridamole group and 133 (52%) in the aspirin plus later extended-release dipyridamole group had no or mild disability (tele-mRS 0 or 1; difference 4-1%, 95% CI -4.5 to 12.6, p=0.45). 28 patients in the early initiation group and 38 in the late initiation group reached the composite endpoint (hazard ratio 0.73, 95% CI 0.44-1.19 p=0.20). Interpretation Early initiation of aspirin plus extended-release dipyridamole within 24 h of stroke onset is likely to be as safe and effective in preventing disability as is later initiation after 7 days.