Triple antiplatelet tx increases bleeding and no better than standard therapy for preventing TIA and recurrent CVA (TARDIS)

Reference

Bath PM, Woodhouse LJ, Appleton JP, et al, for the TARDIS Investigators. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial. Lancet 2018;391(10123):850-859.

Synopsis

Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke (TARDIS) is a multinational multicenter study in which 3100 adults with a noncardioembolic transient ischemic attack (TIA) or acute ischemic stroke were randomized within 48 hours of symptoms to receive intensive antiplatelet therapy ("triple therapy"—consisting of aspirin, clopidogrel, and dipyridamole) or standard guideline-directed therapy with aspirin or clopidogrel plus dipyridamole. Although this was an open-label trial, research staff unaware of treatment allocation performed the outcome assessments 90 days after enrollment. In addition to assessing recurrent stroke or TIA, the researchers evaluated the severity of the events and various measures of function and quality of life. Finally, they also assessed bleeding complications: fatal, major, moderate, minor, and none. The study design called for enrolling 4100 patients; however, the safety and monitoring committee stopped the study early. At the time the trial was stopped, there was no difference in the rate of recurrent events, but 20% of the patients who received triple therapy experienced bleeding compared with 9% of the standard-therapy patients (number needed to treat to harm [NNTH] = 10; 95% CI 8 - 13). Furthermore, the patients who received triple therapy were twice as likely to have major or fatal bleeding (2.5% vs 1.1%; NNTH = 71; 42 - 210).