Clinical Evaluation of Novel Anticoagulants

Abstract

The introduction of direct oral anticoagulants (DOACs) -- dabigatran, rivaroxaban, apixaban, and edoxaban - fundamentally changed anticoagulation therapy over the past decade, offering fixed dosing, no routine monitoring, and fewer food and drug interactions compared to warfarin. Yet real-world clinical experience has revealed complexities that the pivotal trials did not fully anticipate: variable pharmacokinetics in renal impairment, obesity, and extremes of age; uncertain management of DOAC-associated bleeding before specific reversal agents became available; and ongoing debate about which DOAC is optimal for which patient profile. Meanwhile, a new generation of anticoagulants targeting factor XIa (FXIa) -- abelacimab, milvexian, and asundexian -- promises to decouple antithrombotic efficacy from bleeding risk by targeting the intrinsic pathway selectively. We conducted a multicentre retrospective cohort analysis of 6,248 patients across four European centres (Rome, Zurich, Vienna, and Stockholm) receiving anticoagulation for atrial fibrillation (AF, n = 3,824), venous thromboembolism (VTE, n = 1,686), or mechanical heart valves (MHV, n = 738) between January 2015 and December 2021. We evaluated five anticoagulation strategies -- warfarin, dabigatran, rivaroxaban, apixaban, and combined DOAC-switching protocols -- across four clinical endpoints. Our Anticoagulant Clinical Utility Score (ACUS) integrates thromboembolic prevention, major bleeding avoidance, renal safety, patient adherence, and cost-effectiveness. Apixaban achieved the highest ACUS (0.926), driven by the lowest major bleeding rate (2.1% per year) and highest adherence (91.4%), while rivaroxaban showed the best thromboembolic prevention in VTE (recurrence 1.8% per year). We additionally review the phase II data on FXIa inhibitors and project their potential positioning in the anticoagulation landscape.