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By Michael H. Crawford, MD, Editor
SYNOPSIS: A simple protocol for managing atrial fibrillation patients on direct oral anticoagulants perioperatively was shown to produce low levels of major bleeding and thromboembolism for 30 days postoperatively.
SOURCE: Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med 2019; Aug 5. doi: 10.1001/jamainternmed.2019.2431. [Epub ahead of print].
Best practices for interruption of direct oral anticoagulants (DOACs) for elective surgeries or procedures are inconsistent and suffer from a lack of data. Investigators designed the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) multicentered study, with 23 participating centers in Canada, Europe, and the United States. It was a prospective management study with three cohorts: those on apixaban, dabigatran, or rivaroxaban, all used for atrial fibrillation (AF). The interruption/resumption protocol for each agent was based on pharmacokinetic properties of the DOAC, procedure-associated bleeding risk, and the patient’s creatinine clearance (CrCl). Blood samples were taken just before the procedure to measure residual anticoagulation levels later. Heparin bridging was not used. The primary outcomes were major bleeding and arterial thromboembolism for up to 30 days after the procedure. There were 1,257 patients on apixaban, 668 on dabigatran, and 1,082 on rivaroxaban.
The rate of major bleeding was 1.35% for apixaban, 0.90% for dabigatran, and 1.85% for rivaroxaban. In patients undergoing a high bleeding risk procedure, major bleeding occurred in 2.96%, 0.88%, and 2.95%, respectively. The proportion of patients with preoperative DOAC levels of < 50 mg/mL was 90.5%, 95.1%, and 96.8%, respectively. In the subgroups at high bleeding risk, 98.8% registered DOAC levels < 50 mg/mL. The authors concluded that in AF patients on a DOAC undergoing an elective surgery or procedure, a standard perioperative management strategy without heparin bridging or coagulation function testing was associated with low levels of major bleeding (< 2%) and thromboembolism (< 0.5%) over 30 days after procedure. Almost all patients recorded little or no residual anticoagulant levels at the time of the procedure.
The Douketis et al standard perioperative management protocol was simple, resulting in an adherence rate of 95%. For patients undergoing low bleeding risk procedures, stop DOACs one day prior (except for dabigatran with CrCl < 50 mL/min, then stop two days prior). For high bleeding risk patients, stop DOACs two days prior (except for dabigatran with CrCl < 50 mL/min, then stop four days prior). For low bleeding risk procedures, resume DOACs one day after procedure. For high bleeding risk procedures, resume DOACs two to three days after procedure (assuming hemostasis has been achieved). This was a revelation to me, as I have been managing all DOAC AF patients as if they were undergoing a high bleeding risk procedure by this protocol. Considering the excellent data in this study, it would be hard to prove my approach is safer and more effective for preventing thromboemboli. Even minor to mild bleeding was < 10% with Douketis et al protocol.
The big questions are who were these patients, and were they like the ones you and I see? They were relatively similar to AF patients in population studies. Most patients were Caucasian, mean age was about 72 years, two-thirds were male, body mass index averaged around 30 kg/m2, and there were considerable comorbidities. The mean CrCl level was ≥ 78 mL/min, < 15% were on aspirin, < 1% were on a P2Y12 inhibitor, and two-thirds were undergoing a low bleeding risk procedure. These were relatively high-risk patients, with a mean CHA2DS2-VASc score of 3.5 and a mean HASBLED score of 2. Also, this study should be generalizable, as 85% of those screened participated.
However, few received neuraxial anesthesia, and the size of the dabigatran cohort was considerably smaller than the other two DOAC groups. In addition, if, as some believe, the ideal level of a DOAC prior to surgery should be < 30 mg/mL, this was achieved in 93.1% apixaban patients, 98.9% dabigatran patients, and 85.4% rivaroxaban patients. The authors stated that the lower percentage in the rivaroxaban cohort needs further analysis. Finally, patients with venous thromboembolism and those taking edoxaban were not studied. I believe these data are robust enough to change what I recommend for AF patients on a DOAC undergoing elective procedures or surgery. I plan to use the Douketis et al protocol going forward.
Financial Disclosure: Clinical Cardiology Alert’s Physician Editor Michael H. Crawford, MD, Peer Reviewer Susan Zhao, MD, Nurse Planner Aurelia Macabasco-O’Connell, PhD, ACNP-BC, RN, PHN, FAHA, Editor Jonathan Springston, Editor Jason Schneider, Editorial Group Manager Leslie Coplin, and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.