Anticoagulants
Corey Diamond, PharmD
Breakthrough ischemic stroke in patients already treated with DOACs presents a major therapeutic dilemma: Clinicians must decide whether to continue the same drug, adjust the dose, switch to another anticoagulant, or add an antiplatelet agent. Unfortunately, existing guidelines offer little direction.
But a new study, published in the August 2025 issue of Neurology, addresses this gap with data comparing multiple anticoagulation strategies across more than 14,000 patients with AFib who sustained an ischemic stroke while taking a DOAC.
The authors found that strategies based on DOACs performed better than switching to warfarin, particularly for prevention of recurrent ischemic stroke and intracranial hemorrhage. Their findings support a more conservative, patient-centered approach rather than routine conversion to vitamin K antagonists.
Results
Switching from a DOAC to warfarin consistently performed worse than continuing a DOAC-based regimen. Warfarin was associated with an 80% higher rate of recurrent ischemic stroke compared with continuing the same DOAC, and a 72% higher rate compared with dose adjustment of the original agent. Warfarin also produced more intracranial hemorrhage rates, which were 190% higher compared with keeping the same DOAC and 195% higher compared with switching to another DOAC.
Any recurrent stroke occurred more often after conversion to warfarin as well. Ischemic strokes were 102% higher compared with continuing the pre-stroke DOAC and 108% higher compared with dose adjustment. Mortality also rose by 47% when warfarin was used instead of DOAC plus antiplatelet therapy.
Conversely, strategies based on direct oral anticoagulants behaved similarly to one another. Continuing the original drug, switching to another agent, or adjusting the dose resulted in comparable rates of recurrent ischemic stroke, intracranial hemorrhage, and mortality. Adding an antiplatelet agent did not improve outcomes and showed a small trend toward harm for prevention of any recurrent stroke.
Study design
The authors conducted a systematic review and aggregate data meta-analysis through January 2025 and screened 2,171 citations. Eight observational cohort studies met criteria for their analysis. These studies collectively enrolled 14,307 adults who had ischemic stroke while taking a DOAC for AFib. Mean age across cohorts was approximately 75 years, and women accounted for nearly half of participants.
The primary outcome was recurrent ischemic stroke. Secondary outcomes included intracranial hemorrhage, any recurrent stroke, and all-cause mortality. The majority of the included studies were observational, and many were retrospective.
The overall risk of bias was rated as moderate. Consequently, the authors used random effects models for all comparisons because of expected heterogeneity across populations and study settings.
Takeaways
The authors concluded that DOAC-based strategies should remain the default after a breakthrough ischemic stroke, emphasizing that switching to warfarin appears to increase risk across multiple clinically important outcomes. The authors argue that clinicians should focus first on understanding why the stroke occurred.
“Our results suggest the need to tailor the treatment to the patient in all cases of stroke while on DOACs. Simply changing to a different DOAC, changing or adjusting the dose does not clearly reduce the risk of another stroke,” stated the authors in their discussion section.
They later added that the study’s findings “support DOAC-based strategies over warfarin for recurrent stroke prevention in people with atrial fibrillation who have an ischemic stroke while on anticoagulation with DOACs.”
The authors stress that the priority should be identifying reversible contributors such as missed doses, under-dosing, metabolic interference from other drugs, or an alternative cause of embolism.
Ultimately, the study authors recommend that clinicians reconsider rhythm management strategies and ensure comprehensive evaluation of structural and vascular causes. ■