Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Open Heart. 2021 Mar;8(1). doi: 10.1136/openhrt-2020-001471.
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.
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.
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.
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.
ClinicalTrials.gov Registry NCT00412984 and NCT00262600.
生长分化因子 15（GDF-15）是一种与抗凝治疗的心房颤动（AF）患者出血和死亡独立相关的生物标志物。GDF-15 也被用作更精确的基于生物标志物的 ABC（年龄、生物标志物、临床病史）-AF 出血和 ABC-AF 死亡风险评分的一个组成部分。来自大型试验的数据表明，在包括出血和死亡率风险在内的整体结果方面存在地域差异。我们的目的是评估 GDF-15、ABC-AF 出血评分和 ABC-AF 死亡评分与主要出血和死亡之间的关联在世界地理区域之间的一致性。
本队列研究纳入了来自 Apixaban 减少心房颤动血栓栓塞事件（ARISTOTLE）试验的 14767 例 AF 患者和来自随机评估长期抗凝治疗（RE-LY）试验的 8651 例 AF 患者的数据。从随机分组时获得的血浆样本中分析 GDF-15。通过包含与预定义地理区域相互作用的 Cox 回归模型评估结局与 GDF-15、ABC-AF 出血评分和 ABC-AF 死亡评分之间关联的地理一致性。
在两个试验的所有区域中，GDF-15 和 ABC-AF 出血评分与主要出血相关（p<0.0001）。同样，在两个试验的所有区域中，GDF-15 和 ABC-AF 死亡评分与全因死亡率相关（p<0.0001）。总体而言，在 ARISTOTLE 和 RE-LY 试验队列中，GDF-15、ABC-AF 出血评分和 ABC-AF 死亡风险评分与主要出血和死亡之间的关联在各个区域都是一致的。在两个试验队列中，比较不同地理区域时，ABC-AF 出血和 ABC-AF 死亡风险评分的判别能力是一致的。ABC-AF 出血评分的 C 指数范围为 0.649 至 0.760，ABC-AF 死亡评分的 C 指数范围为 0.677 至 0.806。
在接受抗凝治疗的 AF 患者中，GDF-15 和基于生物标志物的 ABC-AF 出血和 ABC-AF 死亡风险评分与主要出血和死亡风险增加相关，并且在全球地理区域具有相似的预后价值。
ClinicalTrials.gov 注册号 NCT00412984 和 NCT00262600。
