Key result
GDF-15 and the ABC-AF risk scores were consistently associated with major bleeding and all-cause mortality across geographic regions (C-indices 0.649-0.760 for bleeding, 0.677-0.806 for death).
Why the study?
Trial data indicate geographic variability in AF outcomes, so the authors aimed to assess the consistency of GDF-15 and ABC-AF risk scores across world regions.
Do GDF-15, the ABC-AF-bleeding score, and the ABC-AF-death score consistently predict major bleeding and death in anticoagulated patients with atrial fibrillation across different geographic regions?
Cohort (n=23,418)
Yes
Do GDF-15, the ABC-AF-bleeding score, and the ABC-AF-death score consistently predict major bleeding and death in anticoagulated patients with atrial fibrillation across different geographic regions?
p-value: p=<0.0001
GDF-15 and the ABC-AF risk scores provide consistent prognostic value for bleeding and mortality in anticoagulated atrial fibrillation patients regardless of geographic region.
Supports consistent prognostic value across regions; extends ABC-AF and GDF-15 validation yet leaves open effects on AF outcomes.
OBJECTIVES: Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions. METHODS: Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region. RESULTS: GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions. CONCLUSIONS: In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry NCT00412984 and NCT00262600.
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Pol et al. (2021) conducted a cohort in atrial fibrillation (n=23,418). GDF-15, ABC-AF-bleeding score, and ABC-AF-death score was evaluated on major bleeding and all-cause mortality (p=<0.0001). GDF-15 and the ABC-AF risk scores were consistently associated with major bleeding and all-cause mortality across geographic regions (C-indices 0.649-0.760 for bleeding, 0.677-0.806 for death).
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