PAUSE study shines light on new standardized perioperative DOAC interruption strategy
A standardized strategy that excludes heparin bridging and pre-operative coagulation testing may be feasible and suitable for individuals with atrial fibrillation (AF) who require interruption of their direct oral anticoagulants (DOACs) prior to elective surgery, results of the PAUSE* study show.
“[U]sing a standardized DOAC-specific perioperative management strategy was safe for patient care, with associated low rates of perioperative major bleeding [<2 percent] and arterial thromboembolism [<1 percent]. Further, a high proportion of patients [>90 percent] had a minimal or no residual DOAC level at the time of the surgery or procedure,” said Professor James Douketis from McMaster University in Ontario, Canada, who presented the findings at ASH 2018.
Study participants were 3,007 adults with AF being treated with DOACs (apixaban [n=1,257, mean age 73.1 years, 64.0 percent male, mean CHADS2 score 2.1], dabigatran [n=668, mean age 72.4 years, 68.6 percent male, mean CHADS2 score 2.2], or rivaroxaban [n=1,082, mean age 72.0 years, 67.0 percent male, mean CHADS2 score 2.0]) who required anticoagulant treatment interruption prior to undergoing an elective surgery or procedure.
Patients undergoing procedures with low bleeding risk had their DOACs ceased for 1 day pre- and post-procedure, while those undergoing high-risk procedures had their DOACs ceased for 2 days pre- and post-procedure. An exception was for dabigatran recipients with creatinine clearance <50 mL/min who had their DOACs ceased for 2 days pre-procedure and 1 day post-procedure for low-risk procedures and for 4 days pre-procedure and 2 days post-procedure for high-risk procedures.
“[This was] a very standardized but importantly, very simple [strategy], because we wanted an array of healthcare professionals and patients to understand and be able to adhere to [it],” said Douketis, noting that 98 and 93 percent of patients adhered to the interruption and resumption schedules, respectively.
A blood sample was taken just prior to the procedure to determine residual DOAC levels and patients were followed up weekly for 4 weeks post-procedure. About one-third of patients (32.3, 34.1, and 34.5 percent of apixaban, dabigatran, and rivaroxaban recipients, respectively) were undergoing procedures with high bleeding risk. Pre-operative coagulation testing was not done nor was heparin bridging, though patients were allowed low-dose heparin as prophylaxis for venous thromboembolism.
Patients on apixaban and rivaroxaban responded to the strategy better than expected with rates of arterial thromboembolism** at 0.16 (95 percent confidence interval [CI], 0–0.48 percent) and 0.37 percent (95 percent CI, 0–0.82 percent), respectively (expected risk was 0.5 percent), with a higher than expected rate in dabigatran recipients (0.60 percent, 95 percent CI, 0–1.33 percent). [ASH 2018, abstract LBA5]
Regarding major bleeding, patients on dabigatran responded better than the 1.0 percent expected rate (0.90 percent, 95 percent CI, 0–1.73 percent), while those on apixaban and rivaroxaban demonstrated higher than expected risk (1.35 [95 percent CI, 0–2.00 percent] and 1.85 percent [95 percent CI, 0–2.65 percent], respectively).
Of the 2,541 patients with pre-operative DOAC levels available, a majority had levels <50 ng/mL (90.5, 95.1, and 96.8 percent of apixaban, dabigatran, and rivaroxaban recipients, respectively). Pre-operative DOAC levels were available for 82.6 percent of patients who underwent high bleeding risk procedures, of whom 98.9 percent had levels <50 ng/mL, with 93.1, 98.9, and 85.3 percent of apixaban, dabigatran, and rivaroxaban recipients, respectively, having “undetectable levels” [<30 ng/mL].
According to Douketis, uncertainty exists regarding the optimal perioperative DOAC management strategy, with questions remaining on the best time to interrupt and resume DOACs, and the requirement for perioperative heparin bridging or perioperative coagulation function testing.
“Since the DOACs were introduced almost 10 years ago, few studies have looked at how to manage these patients … so it’s not surprising that there is a lot of variability in clinical practice and inconsistency around guideline recommendations,” he said.
“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 will establish a standard and will have an effect on clinical practice guidelines,” he said.