A Novel Risk Prediction Score for Atrial Fibrillation

Study Questions:

What is the utility of a novel integer score predictive of a serious net clinical outcome (NCO) in deciding between nonvitamin K antagonist oral anticoagulant (NOAC) and vitamin K antagonist (VKA) treatment in anticoagulation-naïve patients with atrial fibrillation (AF)?


The investigators utilized the VKA-naïve patients from the warfarin arm of the ENGAGE AF-TIMI 48 trial intention-to-treat population to derive the score. ENGAGE AF-TIMI 48 was a randomized clinical trial of edoxaban versus warfarin in 21,105 patients with AF. Cox proportional hazard models identified factors associated with a serious NCO of disabling stroke, life-threatening bleeding, and all-cause mortality in VKA-naïve patients from the warfarin arm. These were used to develop an integer risk score. Performance was assessed by C-indices and validation by bootstrapping. Kaplan–Meier analyses were stratified by three score categories and treatment arm.


Over a median of 2.7 years, 457 NCO events occurred in 2,898 patients with a total person-time of 7,549.5 years (6.05%/year). The risk prediction model (C = 0.693) for the NCO was translated into a 17-point integer score, with annualized event rates for the low-, intermediate-, and high-risk categories in the warfarin arm of 3.5%, 9.9%, and 20.8%, respectively. Therapeutic benefit of higher- and lower-dose edoxaban over warfarin was demonstrated in the high- and intermediate-risk, with equal benefit in the low-risk categories (P-interaction 0.008 and 0.014, respectively).


The authors concluded that in VKA-naïve patients with AF, the TIMI-AF score can assist in the prediction of a poor composite outcome and guide selection of anticoagulant therapy by identifying a differential clinical benefit with a NOAC or VKA.


This study reports that the TIMI-AF score predicted a serious net outcome associated with warfarin therapy in AF patients who are VKA-naïve, and identified high-risk patients who had a favorable treatment benefit with edoxaban compared with warfarin. Edoxaban was associated with improved outcomes for those with intermediate- or high-risk scores, whereas warfarin performed as well as edoxaban with low-risk scores. It should be noted that in VKA-experienced patients, there was no difference in outcomes across risk score categories by treatment arm. While this score may improve risk prediction and help select therapy in anticoagulant-naïve AF patients, it needs to be further validated in additional clinical studies and populations.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Hemorrhage, Risk Assessment, Stroke, Vitamin K, Warfarin

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