Initiating direct oral anticoagulants (DOACs) within four days, rather than at five days or later, after an ischemic stroke in patients with atrial fibrillation (AFib) reduced the risk of future stroke events within 30 days without increasing symptomatic intracerebral hemorrhage, according to CATALYST, a large meta-analysis published June 23 in The Lancet.

For this individual patient data meta-analysis, Hakim-Moulay Dehbi, PhD, et al., pooled patient data from four eligible randomized clinical trials (TIMING, ELAN, OPTIMAS and START) comparing early (within four days) vs. delayed (at five days or later) initiation of DOACs. None of the trials individually proved superiority of early vs. delayed DOAC treatment.

Among the 5,441 participants (78 years old, 46% women), 2,691 had early and 2,750 had delayed DOAC initiation. Most (75%) patients had mild-to-moderate stroke.

Results revealed the primary outcome, a composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage or unclassified stroke within 30 days, occurred in 2.1% of the early vs. 3.0% of the delayed DOAC participants (odds ratio [OR], 0.70; p=0.039). This translated to a number needed-to-treat of 108 to prevent one primary outcome.

Specifically, early vs. later DOAC use lowered the risk of recurrent ischemic stroke (1.7% vs. 2.6%; OR 0.66; p=0.029). Moreover, no increase in symptomatic intracerebral hemorrhage was found with early vs. delayed DOAC treatment (0.4% vs. 0.4%; OR, 1.02; p=0.96).

For the secondary endpoint of the composite outcome at 90 days, there was a numerical reduction with early DOAC initiation, but the between-group difference was not significant.

One limitation of the meta-analysis is that patients with severe stroke and/or hemorrhage "were not well represented in CATALYST, so clinicians must continue to make individualized decisions for these patients," the authors write.

In an accompanying editorial comment, Wendy C. Ziai, MD, MPH, and Georgios Tsivgoulis, MD, PhD, MSc, write that the study "supports the evidence" for early DOAC initiation in AFib-associated ischemic stroke, "especially in patients with smaller infarct size and not at risk for hemorrhagic transformation: better swift than sorry."