Perioperative interruption of direct oral anticoagulants safe, effective

Direct oral anticoagulant interruption before a procedure or surgery using a strategy that considered half-life and procedural bleeding risk appeared safe and effective among patients with prior venous thromboembolism, according to results of a retrospective analysis.

“It has been suggested that the timing of interruption can be decided by considering the underlying bleeding risk of the procedure and the expected half-life of the direct oral anticoagulant based on renal function,” Marc Carrier, MD, MSc, FRCPC, senior scientist in the Clinical Epidemiology Program at The Ottawa Hospital Research Institute, and associate professor of medicine at University of Ottawa, Canada, told HemOnc Today. “Our study suggests that such a management strategy seems to be safe and effective in patients on direct oral anticoagulants for previous VTE.”

Although it is common practice to use direct oral anticoagulants in the setting of VTE, little is known about the risk–benefit ratio and management of their periprocedural interruption in this patient population.

Carrier and colleagues evaluated 190 patients (mean age, 59.1 years) enrolled at The Ottawa Hospital Thrombosis Unit between January 2013 and October 2015 and scheduled to undergo an invasive procedure or surgery. All patients took direct oral anticoagulants — dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Janssen) or apixaban (Eliquis; Bristol-Myers Squibb, Pfizer) — for previous VTE events and required temporary interruption of anticoagulation prior to standard-risk procedures and procedures with increased risk for bleeding. The majority of patients (80.5%) had unprovoked VTE as the most recent event, and 25.3% had recurrent VTE.

Symptomatic VTE rate at 30 days served as the primary efficacy outcome, and major bleeding rate at 30 days served as the primary safety outcome. Secondary outcomes included overall mortality and amount of clinically relevant nonmajor bleeding.

Each treating physician decided on the timing of direct oral anticoagulant interruption and reinitiation. Usual practice is to hold therapy for three half-lives prior to and restart 2 days following standard-bleeding risk procedures, and to hold therapy for five half-lives prior to and restart 4 days following high-bleeding risk procedures.

Mean time from last dose of direct oral anticoagulant to surgery was 56.9 hours for standard-bleeding risk procedures and 69.9 hours for high-bleeding risk procedures. Mean time to therapeutic reinitiation was 47 hours in the standard-bleeding risk group and 80.2 hours in the high-bleeding risk group.

Forty-one percent of patients also received prophylactic doses of low molecular–weight heparin (n = 37) or direct oral anticoagulant (n = 41) in the immediate postoperative period before therapy reinitiation.

Overall, two recurrent VTE events occurred during follow-up — both upper extremity deep vein thromboses — for a 30-day rate of 1.05% (95% CI, 0.29–3.8).

One major bleeding event occurred (30-day rate, 0.53%; 95% CI, 0.09–2.93) in a patient undergoing major cancer surgery for resection of locally advanced rectal cancer.

No deaths (0%; 95% CI, 0-1.98) occurred during the 30-day follow-up period.

Six clinically relevant nonmajor bleeding events occurred — two led to temporary cessation of anticoagulation and one required medical intervention — for a rate of 3.16% (95% CI, 1.46–6.72). Two of these occurred during the immediate postoperative period. – by Melinda Stevens

For more information:

Marc Carrier, MD, MSc, FRCPC , can be reached at The Ottawa Hospital, General Campus, Department of Medicine, Division of Hematology, 501 Smyth Road, Box 201A, Ottawa, ON K1H 8L6, Canada; email: mcarrier@toh.ca.

Disclosures: Carrier reports consultancy fees from Bayer and Boehringer Ingelheim, and research funding from Bristol-Myers Squibb. One other researcher reports research funding from Portola.