Raschi Emanuel, Bianchin Matteo, Ageno Walter, De Ponti Roberto, De Ponti Fabrizio
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio, 48, I-40126, Bologna, Italy.
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Drug Saf. 2016 Dec;39(12):1175-1187. doi: 10.1007/s40264-016-0464-3.
Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from 'real-world' postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk-benefit profile of DOACs in the aforementioned consolidated indications through an 'evidence summary' approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.
自2008年以来，直接口服抗凝剂（DOACs）扩大了心血管疾病的治疗选择范围，对非瓣膜性心房颤动（NVAF）和静脉血栓栓塞症（VTE）等具有公认临床和流行病学影响的疾病，以及在骨科手术患者的预防方面都有应用。大量证据，不仅来自关键临床试验，还来自迄今收集的“真实世界”上市后观察结果（如分析性流行病学研究和登记数据），使得首次尝试事后验证DOACs的药理学优势是否真的转化为治疗创新成为可能，这对临床医生、监管机构和患者都有相关影响。本综述旨在通过“证据总结”方法，收集现有循证数据，特别是对随机对照试验进行荟萃分析的系统评价以及观察性研究，比较DOACs与维生素K拮抗剂，来综合分析DOACs在上述既定适应症中的风险效益概况。将讨论临床证据并与主要国际指南进行比较，以确定是否需要更新。还将研究有争议的临床相关安全问题，以突出当前的挑战和未解决的问题（如易感人群的实际出血风险）。预计关于NVAF或VTE的大量出版物（我们分析中保留了44项进行荟萃分析的系统评价和12项观察性研究）表明可能存在重叠研究，需要共同标准来定性和定量评估不一致之处，从而指导未来的研究。
