Raschi Emanuel, Bianchin Matteo, De Ponti Roberto, De Ponti Fabrizio, Ageno Walter
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Pharmacol Res. 2017 Jun;120:206-218. doi: 10.1016/j.phrs.2017.03.026. Epub 2017 Mar 31.
Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories.
直接口服抗凝剂（DOACs）因其被视为创新的药理特性，被认为可能会在需要短期和长期抗凝治疗的患者的治疗方案中引发潜在的范式转变。迄今为止收集到的证据（从批准前的关键试验到上市后真实世界的观察数据）一致证实，DOACs在安全性、有效性和疗效方面总体上与维生素K拮抗剂（VKAs）相当，并明确记录了在非瓣膜性心房颤动（NVAF）和静脉血栓栓塞（VTE）情况下颅内出血风险持续且具有临床相关性的降低。有趣的是，在当前的研究场景中可以识别出两条平行的路径：A）在上述已确立的治疗适应症中，一种创新方法是针对个性化治疗策略，以确定最有可能从不同抗凝药物之一中获益的患者，特别是不良事件（如出血）风险增加的亚组；B）在非传统环境中，DOACs在以动脉和静脉血栓栓塞风险为特征的新兴疾病中的潜在用途正受到关注。在这些情况下，与VKAs或肝素相比，DOACs的风险效益概况尚不太明确。本综述的目的是严格评估DOACs新兴治疗用途（如肝素诱导的血小板减少症、抗磷脂抗体综合征）的证据基础，包括特殊人群（如VTE与癌症或肝硬化患者）中不断演变的问题。这将通过分析主要公共数据库中已发表和未发表证据的强度（即系统评价、随机临床试验、观察性研究、病例报告/系列）和一致性（即一致性）来实现。
