Key Points:
- The ABC-AF trial evaluated whether treatment recommendations based on biomarker-based risk scores could improve outcomes compared with standard guideline-based care in patients with atrial fibrillation (AF).
- Tailored management using the ABC-AF stroke and bleeding scores did not reduce the risk of stroke, death, or major bleeding.
- These results highlight the importance of validating precision medicine tools in prospective trials before routine clinical implementation.
Patients with atrial fibrillation (AF) are at elevated risk of stroke and often require oral anticoagulation (OAC). Although several validated biomarker-based risk scores (e.g., ABC-AF-stroke and ABC-AF-bleeding) have been developed to estimate individualized risk, their utility for guiding treatment decisions has not been rigorously tested in real-world clinical settings.
The ABC-AF trial, presented at ESC Congress 2025 and simultaneously published in Circulation, was a pragmatic, registry-based, randomized controlled trial designed to evaluate whether tailoring AF treatment based on individual ABC-AF risk scores could improve outcomes versus usual guideline-directed care.
Conducted across 39 Swedish sites, the open-label trial enrolled 3,933 patients with a median age of 73.9 years (34% women). Participants included those with both newly diagnosed and existing AF, with or without current OAC treatment. Patients were randomized 1:1 to receive either ABC-AF score-guided treatment or standard of care. In the intervention arm, plasma biomarkers were measured and risk scores calculated, and investigators received treatment recommendations based on individualized stroke and bleeding risk profiles. The primary outcome was a composite of stroke or death.
After a median follow-up of 2.6 years, the primary outcome occurred at a similar rate in both groups: 3.18 vs. 2.67 events per 100 patient-years (HR 1.19; 95% CI 0.96–1.48; p=0.12). There were no significant differences in the rates of stroke (HR 1.18; p=0.44), death (HR 1.21; p=0.13), or major bleeding (HR 1.08; p=0.50).
Although OAC use increased more in the active arm (97.8% vs. 92.6%), and there were shifts in the types of OACs used (increased apixaban and dabigatran, decreased rivaroxaban and warfarin), these changes did not translate into improved outcomes. Antiplatelet use decreased and statin use increased similarly in both groups.
Recruitment was stopped early due to a non-significant trend toward increased mortality in patients with CHA2DS2-VASc ≥3 in the intervention arm. Investigators noted that lower-than-expected event rates and underpowering may have limited the ability to detect a benefit.
“We found no benefit of individually tailored, multidimensional treatment recommendations based on ABC-AF-stroke and ABC-AF-bleeding scores compared with usual care,” said principal investigator Professor Jonas Oldgren (Uppsala University). “These findings emphasize the need for prospective testing of risk stratification tools in clinical settings before widespread implementation.”
Funded by the Swedish Research Council, the Swedish Heart-Lung Foundation, and Roche Diagnostics, ABC-AF underscores the importance of rigorous validation of personalized treatment strategies in AF.
