Written by Peter Liu
Spoon Feed
In patients with atrial fibrillation (AF) and spontaneous intracranial hemorrhage (ICH), direct oral anticoagulants (DOAC) decreased risk of ischemic stroke (NNT=13) but increased risk of ICH (NNH=24).
For AF + ICH, the risk-benefit balance is uncertain in the DOAC era
A simplified framework for treatment of atrial fibrillation is as follows:
- Prevent stroke, most commonly with anticoagulation therapy.
- Reduce and prevent AF symptoms through a rate or rhythm control strategy.
- Prevent adverse cardiovascular outcomes such as tachycardia-associated heart failure, myocardial infarction, and death.
For patients with an estimated stroke risk greater than 2% per year (CHADSVASC score >2), anticoagulation is usually recommended. However, the risks of anticoagulant therapy include increased pill burden, nuisance bleeding, major GI and non-GI bleeding, and intracranial hemorrhage (ICH), from least to most serious. The idea of causing hemorrhagic stroke to prevent ischemic stroke is particularly troubling, prompting most clinicians to avoid anticoagulation in patients with a history of ICH.
The PRESTIGE-AF was a randomized controlled trial of DOAC vs. no therapy on this high-bleeding-risk patient population. Among 319 patients with AF and spontaneous ICH not due to vascular malformation, DOACs reduced first ischemic strokes (HR 0.05; 95%CI 0.01–0.36; p<0.0001), but failed non-inferiority for recurrent ICH (HR 10.89; 90%CI 1.95–60.7; ARI 4.2 per 100 patient-years). Ischemic stroke rates were 0.83 vs. 8.60 events/100 patient-years favoring DOACs, whereas ICH rates were higher with DOACs (5.00 vs. 0.82 events/100 patient-years). These findings generally suggest fairly comparable ICH risks to ischemic CVA benefit.
How does this change my practice?
For patients with AF and very high risk for bleeding and stroke, I strongly favor management by a clinician with expertise in both atrial fibrillation as well as procedures to mitigate stroke risk, such as left atrial appendage occlusion (LAAO). While results from PRESTIGE-AF may suggest a possible, razor-thin marginal benefit of DOAC therapy for patients with AF and ICH, most of these patients warrant consideration for LAAO. Outside of LAAO considerations, decisions regarding AC therapy should be individualized and made with a high level of caution.
Source
Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral hemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2025 Mar 15;405(10482):927-936. doi: 10.1016/S0140-6736(25)00333-2. Epub 2025 Feb 26. Erratum in: Lancet. 2025 Mar 15;405(10482):896. doi: 10.1016/S0140-6736(25)00466-0. PMID: 40023176
