In frail elderly patients who are stable on warfarin for stroke prevention from atrial fibrillation, can you switch them to a DOAC? And does that lead to harm?¶
Answer: Switching is probably reasonable for most, but monitor closely in the first ~60 days and prefer apixaban.
- Background: DOACs are standard of care for stroke prevention in AF requiring anticoagulation (multiple RCTs).
- FRAIL-AF (large open-label RCT): in frail older adults already stable on a VKA, switching to a DOAC may lead to more bleeding without a reduction in thromboembolic events.
- Caveats of FRAIL-AF — early termination (can overestimate treatment effect), and early overlap of DOAC and VKA exposure (investigators addressed this after the first 102 patients were randomized). Two further points from the critique in Can J Cardiol:
Although subgroup analysis provided no statistical evidence for heterogeneity of treatment effect, the hazard ratio for bleeding with individual DOACs ranged from 1.10 to 2.17 and the confidence levels were wide, so a type 2 error cannot be excluded.
The population of FRAIL-AF was stable while receiving a VKA and monitored in a specialized anticoagulant clinic. Therefore, the results might not apply to recently diagnosed AF in patients with frailty, nor even to stable patients receiving a VKA who are managed in a community setting
- Conflicting later evidence:
- COMBINED-AF — individual-patient-data systematic review and meta-analysis of the landmark AF trials plus COMBINE-AF (~6000 frail patients): less stroke/systemic embolism, fatal bleeding, intracranial hemorrhage, and death with DOACs.
- Retrospective database study (~165,000 patients): switching to apixaban performed very well, while switching to rivaroxaban led to more bleeding; most of the excess risk occurred within the first 60 days.
- Bottom line: switching is probably OK, but monitor closely within the first 60 days. Apixaban preferred.