Clinical Studies with Anticoagulants that Have Changed Clinical Practice

Abstract

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.

2024 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

“…Consequently, the most popular papers from each category are identified separately. Tables 3 and 4 respectively list the top 25 downloaded articles from STH in 2023 (from 2022 and 2023 inclusive), as eligible for either the “free access” ( Table 3 ) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 or “general category” ( Table 4 ) 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 awards.…”

Approaches to Precision‐based Anticoagulation management in the critically Ill

“…The approval and implementation of anticoagulants and their reversal agents are based on clinical trials as well as published experiences from retrospective cohort analyses ranging from individual institutions to large databases. Similar to other areas of medicine, the real‐world clinical challenges for utilization of anticoagulant and hemostatic medications, especially in the critically ill, often occur in patients who were not included in the studies which garnered the approval of these agents 1 . Anticoagulant and hemostatic medications are often utilized for multiple conditions that are not within the approved indications or explored in controlled clinical trials 2–7 .…”

“…Similar to other areas of medicine, the real-world clinical challenges for utilization of anticoagulant and hemostatic medications, especially in the critically ill, often occur in patients who were not included in the studies which garnered the approval of these agents. 1 Anticoagulant and hemostatic medications are often utilized for multiple conditions that are not within the approved indications or explored in controlled clinical trials. [2][3][4][5][6][7] In the critically ill, multiple drivers leading to higher risks for thrombosis and bleeding exist where clinicians have to carefully assess, implement, and alter management plans as the patient's acuity progresses or recovers.…”

Greats in the History of Thrombosis and Hemostasis

“…Hence, it was judicious to read the recent contribution from Hirsh et al, 3 Favaloro, 1 and other well-referenced distinguished experts in the field of thrombosis and hemostasis. 4 5 I respectfully endorse the recent series of historical publications in this journal and encourage the existing and emerging members in the field to acquire pertinent knowledge from these celebrated scholars, investigators, and mentors who have passionately dedicated their professional careers to enhance our understanding of the complex intricacies of thrombosis and hemostasis.…”