SUMMARY: Direct Oral AntiCoagulants (DOACs) are often prescribed for thromboembolic events. This class of anticoagulants, have a rapid onset and offset of action, short half-life, predictable anticoagulant effects, no laboratory monitoring and fixed dosing schedule. The half-life of these agents can however be prolonged in those with renal insufficiency and may be unsafe and direct oral anticoagulants are ineffective in patients with mechanical heart valves. In several clinical studies, DOACs have been shown to reduce the rate of major bleeding by 28% and the rates of intracranial and fatal hemorrhage by 50%, when compared to COUMADIN® (Warfarin).
It is estimated that each year 10-15% of patients on DOACs will undergo an invasive procedure or surgery and will require temporary interruption of anticoagulation prior to standard-risk procedures and procedures with increased risk for bleeding. There are presently five DOACs approved in the US. They include PRADAXA® (Dabigatran), which is a Direct Thrombin Inhibitor and XARELTO® (Rivaroxaban), ELIQUIS® (Apixaban), SAVAYSA® (Endoxaban), BEVYXXA® (Betrixaban) which are Factor Xa inhibitors.
The perioperative management of patients who are taking a Direct Oral AntiCoagulant (DOAC) for Atrial Fibrillation and require an elective surgery/procedure, has remained unclear, as there is no published data on the timing of perioperative DOAC interruption and resumption, and if perioperative Heparin bridging and coagulation function testing before surgery are needed. The purpose of the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study was to establish a simple protocol that did not require perioperative anticoagulant bridging or coagulation function testing.
PAUSE is a prospective study of DOACs, which included 3 parallel cohorts of patients with Atrial Fibrillation taking ELIQUIS® (N=1257), PRADAXA® (N=668) or XARELTO® (N=1082), and requiring anticoagulant interruption for an elective surgery/procedure. This current analysis included patients from Canada, U.S. and Europe. A third of the patients (33.5%) were scheduled to undergo a high-bleeding risk surgery and the adjusted stroke risk among these patients was about 4.5%, based CHADS2 scores. The mean patient age was 72.5 years and 66% of patients were men.
The researchers in this study used a standardized protocol based on pharmacokinetic properties of the DOACs, procedure-associated bleeding risk, Creatinine Clearance, and held DOACs for 1 day before and 1 day after surgery for procedures with low bleeding risk, and for 2 days before and 2 days after for procedures with high bleeding risk. Patients on PRADAXA® with a creatinine clearance of less than 50 mL/min and who were planned for a procedure with a high bleeding risk, stopped the drug four days before and two days after surgery. Blood samples were obtained just before the procedure to measure residual DOAC levels. Bridging with Heparin and preoperative coagulation testing were not used to manage patients. Participants were followed weekly for 30 days post-procedure to measure incidence of major bleeding and Arterial ThromboEmbolism, which was the Primary endpoint.
The 30-day postoperative major bleeding rates were 1.35% in the ELIQUIS® group, 0.9% in the PRADAXA® group and 1.85% in the XARELTO® group. The rate of Arterial ThromboEmbolism was 0.16% in the ELIQUIS® group, 0.6% in the PRADAXA® group and 0.37% in the XARELTO® group. The researchers also measured preoperative DOAC levels in 85% of patients and noted that 99% of these patients having a high bleeding risk procedure had DOAC levels less than 50 ng/mL.
It was concluded that a standardized DOAC-specific perioperative management strategy was safe for patient care among patients with Atrial Fibrillation, who were taking a DOAC and required anticoagulant interruption for an elective surgery/procedure. Utilizing this standardized protocol was associated with low rates of perioperative major bleeding (less than 2%) and Arterial ThromboEmbolism (less than 1%). The authors added that PAUSE is the largest practice-changing study to date, that addresses perioperative DOAC management, and will very likely establish a treatment standard, impacting practice guidelines in perioperative care. Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study: A Perioperative Management Plan for Patients with Atrial Fibrillation Who Are Receiving a Direct Oral Anticoagulant. Douketis J, Spyropoulos AC, Duncan JM, et al. Abstract LBA-5. Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA.