Researchers have developed a “simple, standardized, easy-to-use” strategy to guide decisions about interrupting direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) scheduled to undergo an elective surgery or procedure. The approach was safe and associated with a low incidence of perioperative major bleeding and arterial thromboembolism.
“This is a common clinical problem that occurs in one in six patients with atrial fibrillation each year, or six million patients worldwide, and it is increasing in prevalence as the population ages,” reported James Douketis, MD, from McMaster University in Ontario, who presented the results of the late-breaking trial at the 2018 ASH Annual Meeting. However, “since the DOACs were introduced nearly 10 years ago, few studies have looked at how to manage these patients, [leading to] a lot of variability in clinical practice and inconsistency in guideline recommendations.”
The aim of the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study, Dr. Douketis said, was to establish a simple tool that did not require perioperative anticoagulant bridging or coagulation function testing.
Interruption and resumption of DOACs was dictated by the bleeding risk associated with the planned procedure and the type of DOAC: For procedures with low bleeding risk (e.g., colonoscopy or hernia repair), DOACs were interrupted for one day before and one day after surgery; for procedures with high bleeding risk (e.g., major cancer, heart, or orthopedic surgery), DOACs were interrupted for two days before and two days after surgery. Patients on dabigatran with a creatine clearance <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.
Researchers evaluated the approach in 3,007 patients with AF receiving apixaban (n=1,257), dabigatran (n=668), or rivaroxaban (n=1,082). Approximately one-third of patients in the trial were scheduled to undergo a high-bleeding-risk surgery, and the median CHADS2 scores (a 1- to 5-point scale measuring stroke risk based on congestive heart failure, hypertension, age, diabetes, and previous stroke) were 2.1, 2.2, and 2.0 in the apixaban, dabigatran, and rivaroxaban groups, respectively.
Participants were followed weekly for 30 days post-procedure to measure incidence of major bleeding and arterial thromboembolism (primary endpoint).
The researchers expected arterial thromboembolism (including stroke, systemic embolism, and transient ischemic attack) to occur in 0.5 percent of patients and major bleeding in 1 percent. They reported lower-than-expected rates for arterial thromboembolism in the entire cohort, but the rates were higher than expected in the apixaban and rivaroxaban groups (TABLE).
An analysis of preoperative blood samples indicated that more than 90 percent of patients treated per the PAUSE protocol had minimal or no residual DOAC levels. Nearly all patients (98.9%) undergoing a high-bleeding-risk procedure had DOAC levels <50 ng/L, prompting the investigators to select 50 ng/L as “a clinically safe threshold to allow a surgery to proceed.”
“This is the first study to demonstrate the safety of a standardized perioperative management approach in patients with AF who are taking a DOAC, and we hope it will establish a standard and will have an effect on clinical practice guidelines,” Dr. Douketis concluded.
The authors report financial relationships with Pfizer, Janssen, Merck, Aniara-Hyphen Biomed, and Sanofi.
Douketis J, Spyropoulos AC, Duncan JM, et al. Perioperative anticoagulant use for surgery evaluation (PAUSE) study: a perioperative management plan for patients with atrial fibrillation who are receiving a direct oral anticoagulant. Abstract LBA-5. Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA.