Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Heart Center, Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Semin Thromb Hemost. 2023 Apr;49(3):242-254. doi: 10.1055/s-0042-1760330. Epub 2023 Jan 5.
Anticoagulant therapy is the cornerstone of treatment and prevention of arterial and venous thromboembolism. Taking a historical perspective, starting in the 1960s, and progressing through to 2022, we discuss key clinical trials of anticoagulants that have changed clinical practice, and examine obstacles encountered in bringing these anticoagulants to the clinic. The design of some of the early studies that shaped clinical practice was poor by current standards, but their results were influential because nothing better was available. Both heparin and vitamin K antagonists had been in clinical use for several decades before well-designed trials in the 1980s optimized their dosing and enhanced their safety and efficacy. Low-molecular-weight heparin then replaced unfractionated heparin because it had a more predictable dose-response and a longer half-life, thereby allowing it to be used conveniently in out-of-hospital settings. More recently, direct oral anticoagulants became the oral anticoagulants of choice for most indications because they were shown to be at least as safe and effective as vitamin K antagonists when used in fixed doses without the need for laboratory monitoring. The design of the trials that led to the approval of the direct oral anticoagulants was excellent, but further studies are required to optimize their dosing in selected patients who were underrepresented in these trials.
抗凝治疗是治疗和预防动静脉血栓栓塞症的基石。从历史的角度来看，从 20 世纪 60 年代开始，一直到 2022 年，我们讨论了改变临床实践的关键抗凝临床试验，并研究了将这些抗凝剂推向临床所遇到的障碍。一些早期的研究设计按照现在的标准很差，但它们的结果很有影响力，因为没有更好的方法。肝素和维生素 K 拮抗剂在 20 世纪 80 年代进行了精心设计的试验，优化了剂量，提高了安全性和有效性，在此之前，它们已经在临床上使用了几十年。低分子量肝素随后取代了未分级肝素，因为它具有更可预测的剂量反应和更长的半衰期，从而可以在院外环境中方便地使用。最近，直接口服抗凝剂成为大多数适应证的首选口服抗凝剂，因为与维生素 K 拮抗剂相比，在固定剂量下使用时，它们至少同样安全有效，而无需实验室监测。导致直接口服抗凝剂批准的试验设计非常出色，但需要进一步研究来优化这些试验中代表性不足的特定患者的剂量。
