Biomarker-based ABC-AF Risk Scores for Personalized Treatment to Reduce Stroke or Death in Atrial Fibrillation – a Registry-based Multicenter Randomized Controlled Study

The clinical utility of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score-guided multidimensional treatment strategy improves long-term outcomes in patients with atrial fibrillation (AF). The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the active arm, the investigator was informed of each individual's ABC-AF-score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct OAC. In the control arm, patient management was at the discretion of the investigator. Primary outcome was a composite of stroke or death. Secondary outcomes included stroke, death, major bleeding events, and their composite outcome. The intention-to-treat population comprised 3933 patients, median age 73.9 years, 33.6% women, 51.3% had paroxysmal AF, 11.2% had prior stroke or TIA, and 85.7% had OAC treatment. After randomization, 97.8% in active and 92.6% in control arm received OAC, p<0.0001. Enrollment was prematurely terminated owing to safety concerns with a trend towards higher mortality in patients with CHA2DS2-VASc scores of 3 or above, and the study was therefore underpowered for its primary objective. Over a median follow-up of 2.6 years, 175 primary events (3.18/100 patient-years [100PY]) occurred in the active and 148 (2.67/100PY) in the control arm, hazard ratio with 95% confidence interval (HR) 1.19, 0.96-1.48, p=0.12. Major bleeding events were 152 (2.82/100PY) versus 141 (2.61/100PY), HR 1.08; 0.86-1.36, p=0.50; stroke 48 (0.87/100PY) versus 41 (0.74/100PY), HR 1.18, 0.78-1.79, p=0.44; death 136 (2.44/100PY) versus 113 (2.02/100PY), HR 1.21, 0.94-1.55, p=0.13, and rates of the composite stroke, death, or major bleeding 277 (5.21/100PY) versus 244 (4.55/100PY), HR 1.14; 0.96-1.36, p=0.13. Primary outcome results were similar across ABC-AF-score subgroups (interaction p=0.98). The individually tailored multidimensional treatment strategy, based on ABC-AF risk scores, did not improve clinical outcomes as compared with usual guideline-based care in patients with AF. The results emphasize the need for prospective testing of the utility of risk stratification and precision medicine tools in different clinical settings before implementation in routine care.