Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany.
Cerebrovasc Dis. 2013;36(2):115-9. doi: 10.1159/000352062. Epub 2013 Sep 11.
The novel direct oral anticoagulants (NOA), dabigatran (a thrombin inhibitor), rivaroxaban and apixaban (factor Xa inhibitors) have shown at least noninferiority compared to warfarin concerning the prevention of stroke and systemic embolism as well as the risk of hemorrhagic complications in large phase III trials in patients with atrial fibrillation (AF). These results have been obtained under regular monitoring of side effects and reinforcement of medication adherence in carefully controlled clinical trials. To what extent they translate into clinical practice is a matter of ongoing research. While postmarketing registers, most prominently the GLORIA-AF registry, are currently recruiting and will not report data for several years, we aimed at extracting risk factors for hemorrhagic complications under NOA from all available case reports and single case series published to date.
To identify risk factors which increase the risk of hemorrhage under NOA, we performed a PubMed search for both dabigatran and rivaroxaban, as well as three search terms for hemorrhagic complications. The cases of hemorrhagic complications were analyzed for the presence of the following four factors: 'prescriber errors', 'unfavorable comedications', 'renal impairment' and 'prescription of NOA in the frail elderly'.
We found a discrepancy in the frequency of case reports on hemorrhagic complications to the disadvantage of dabigatran which can hardly be attributed to the earlier marketing time of dabigatran alone. As risk factors, we identified prescriber errors, impaired renal function, comedication with antiplatelet drugs or p-glycoprotein inhibitors, old age and low body weight. Strikingly, the majority of the bleeding complications reported in this compilation of case reports showed at least one and in most cases several risk factors.
We should, therefore, carefully select our patients for treatment with the NOA with an emphasis on age, body weight, renal function and comedications and follow them faithfully concerning their medication adherence and eventual side effects.
新型口服抗凝药物（NOA），达比加群（凝血酶抑制剂）、利伐沙班和阿哌沙班（因子 Xa 抑制剂），在 III 期临床试验中与华法林相比，在预防房颤（AF）患者的中风和全身性栓塞以及出血并发症风险方面显示出至少非劣效性。这些结果是在对副作用进行常规监测和加强药物依从性的情况下，在精心控制的临床试验中获得的。它们在多大程度上转化为临床实践是一个正在研究的问题。虽然上市后登记处，特别是 GLORIA-AF 登记处，目前正在招募，并且在几年内不会报告数据，但我们的目的是从迄今为止发表的所有可用病例报告和单个病例系列中提取 NOA 下出血并发症的危险因素。
为了确定 NOA 下出血风险增加的危险因素，我们对达比加群和利伐沙班进行了 PubMed 搜索，并对三个出血并发症的搜索词进行了搜索。对出血并发症病例进行了分析，以确定以下四个因素的存在：“处方错误”、“不利的合并用药”、“肾功能不全”和“在体弱老年人中开具 NOA 处方”。
我们发现，出血并发症的病例报告频率存在差异，对达比加群不利，这很难归因于达比加群的早期上市时间。作为危险因素，我们确定了处方错误、肾功能不全、与抗血小板药物或 P-糖蛋白抑制剂合并用药、年龄较大和体重较低。引人注目的是，本病例报告汇编中报告的大多数出血并发症至少有一个，在大多数情况下有几个危险因素。
因此，我们应该仔细选择我们的患者接受 NOA 治疗，重点关注年龄、体重、肾功能和合并用药，并忠实于他们的药物依从性和最终的副作用。
