Beshir S A, Aziz Z, Yap L B, Chee K H, Lo Y L
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
National Heart Institute, Kuala Lumpur, Malaysia.
J Clin Pharm Ther. 2018 Apr;43(2):209-219. doi: 10.1111/jcpt.12634. Epub 2017 Oct 13.
Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients.
The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed.
A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic = 0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events.
To the best of our knowledge, this is the first evaluation study of the predictive performance of these 6 BRSs on clinically relevant bleeding events applied to the same cohort consisting of mainly Asian novel oral anticoagulant users. These BRSs show poor to acceptable predictive performance on OAC-induced major or CRB events. An improvement in the existing BRSs for OAC users is warranted.
出血风险评分（BRS）有助于评估心房颤动患者口服抗凝剂相关的出血风险。理想情况下，在将BRS常规应用于原始推导队列以外的人群之前，需要评估其适用性。因此，我们评估了6种既定的BRS在预测马来西亚患者使用口服抗凝剂（OAC）相关的严重或临床相关出血（CRB）事件方面的性能。
回顾了两家三级医院接受华法林、达比加群或利伐沙班治疗的非瓣膜性心房颤动（NVAF）患者的药房供应数据库和病历。确定在随访12个月内发生OAC相关严重或CRB事件的患者，或接受OAC治疗至少1年的患者。将BRS分别应用于患者数据。然后评估这些BRS的辨别能力和校准情况以及与出血事件相关的因素。
共招募了1017名至少随访1年的患者，或在使用OAC 1年内发生出血事件的患者。其中，23名患者发生了首次严重出血事件，76名患者发生了首次CRB事件。多因素逻辑回归结果显示，75岁及以上、既往出血和男性与严重出血事件相关。另一方面，既往胃肠道出血、血细胞比容值低于30%和肾功能损害是CRB事件的独立预测因素。所有BRS对严重和CRB事件均显示出令人满意的校准。在这些BRS中，只有HEMORR HAGES（C统计量=0.71，95%CI 0.60-0.82，P<.001）和ATRIA评分（C统计量=0.70，95%CI 0.58-0.82，P<.001）在严重出血事件方面显示出可接受的辨别性能。然而，所有6种BRS在CRB事件方面均缺乏可接受的预测性能。
据我们所知，这是对这6种BRS在应用于主要由亚洲新型口服抗凝剂使用者组成的同一队列的临床相关出血事件预测性能的首次评估研究。这些BRS在OAC引起的严重或CRB事件方面显示出较差至可接受的预测性能。有必要改进现有的OAC使用者BRS。
