Perioperative Management of Patients on the New Oral Anticoagulants

Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE)

NCT02228798

McMaster University

Canadian Institutes of Health Research (CIHR) Heart and Stroke Foundation of Canada

15-20 medical centers in North America

3,291 patients

Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) is a prospective, multicenter cohort study of patients who are currently taking dabigatran, rivaroxaban, or apixaban for oral anticoagulation used for stroke prevention in atrial fibrillation, and who require its temporary interruption for a surgical or invasive procedure. Participants will receive pre- and postprocedure target-specific oral anticoagulants (TSOACs) according to a protocol that is standardized but adjusted according to patients’ renal function and the surgery/procedure-related bleed risk. Heparin bridging will not be administered.

The TSOACs dabigatran, rivaroxaban, and apixaban are used for stroke prevention in atrial fibrillation (AF) and to prevent and treat venous thromboembolism (VTE). After multiple large randomized controlled trials, we now know that for most patients with VTE or AF, the TSOACs are at least as safe and effective as standard anticoagulant therapies used for these conditions. Although secondary analyses (Healey JS et al. Circulation. 2012;126:343-348; Sherwood MW et al. Circulation. 2014;129:1850-1859) have used data from the phase III registration trials of the TSOACs to describe the periprocedural risk of stroke and bleeding, none of those trials used a standardized protocol to guide perioperative TSOAC management. Thus, decisions about whether and when to interrupt and resume TSOACs around procedures and about whether to use heparin bridging were left to the discretion of the local investigator. Not surprisingly, periprocedural anticoagulation management varied widely, both within and across the trials, and none of those studies assessed the effect of the timing of TSOAC interruption on assays of coagulation function — testing which could be important prior to major surgery and/or spinal anesthesia.

For patients who have experienced (or are at risk for) thromboembolism, the TSOACs offer advantages over warfarin. They have been approved without the need for routine measurement of their anticoagulant effect and, compared with vitamin K antagonists, have much less potential for drug-drug and drug-diet interactions. Perhaps no hypothetical advantage of the TSOACs is more important than the possibility that these medicines may eliminate the need for periprocedural heparin bridging. The short half-life and rapid onset of action that are characteristics of each TSOAC will minimize the time that a patient who needs a procedure is without anticoagulation. The PAUSE study will tell us when we should interrupt and re-start TSOACs in patients who undergo procedures and will provide data on how various measures of coagulation function change after a TSOAC is interrupted.