Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study

Abstract

Background: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrilla-tion (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin-K-antagonists (VKA) regarding hemorrhagic complications. Aims: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. Methods: PRODAST is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within three months after early (≤7 days) or late (>7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. Results: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95%CI: 0.10-2.21) for early dabigatran use vs VKA use and an adjusted HR of 0.09 (95%CI: 0.00-13.11) for late dabigatran use vs VKA use. No differences were found between early initiation of dabigatran vs VKA use regarding ischemic endpoints. Conclusions: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate. Registration: ClinicalTrials.gov Identifier: NCT02507856.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage

“…The ELAN trial and a subsequent meta-analysis also suggested that it was safe to start DOAC therapy early compared with delayed initiation [ 139 , 141 ]. A recent analysis of the PRODAST study included 3312 patients with acute IS or transient ischemic attack (TIA) who were treated with dabigatran or VKA and indicated that the early (≤ 7 days) initiation of dabigatran seemed to be safer and superior than VKA initiated at any time with regards to the risk of ICH [ 142 ]. Anyway, the timing of restarting anticoagulation varies greatly amongst centers and regions.…”