Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

Abstract

IMPORTANCE Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. OBJECTIVE To investigate the safety of a standardized perioperative DOAC management strategy. DESIGN, SETTING, AND PARTICIPANTS The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. INTERVENTIONS A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. MAIN OUTCOMES AND MEASURES Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure. RESULTS The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. CONCLUSIONS AND RELEVANCE In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

Dental extractions on direct oral anticoagulants vs. warfarin: The DENTST study

“…Therefore, we do not recommend measuring DOAC drug levels prior to dental extractions to predict bleeding outcomes. Our findings support the current practice of standardized perioperative DOAC management based on the drug’s pharmacokinetic properties and type of surgical procedure, rather than drug levels …”

“…Our findings support the current practice of standardized perioperative DOAC management based on the drug's pharmacokinetic properties and type of surgical procedure, rather than drug levels. 19,20 We recognize that this study has a number of limitations. First, as the sample size of each cohort was limited to the eligible patients who presented to our department and provided informed consent, sample size calculations were not performed.…”

Scientific and Standardization Committee Communication: Guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: Recommendations for standardized reporting of procedural/surgical bleed risk and patient‐specific thromboembolic risk

“…19 More recently, preliminary results from the large, multicenter PAUSE trial assessing standardized DOAC interruption for an elective procedure or surgery also found a 30-day MB rate of 1.43% (95% CI: 0-1.83). 24 The bleed risk stratification of procedures and surgeries requiring OAC interruption into non-high bleed risk vs high bleed risk is important because the anticipated background event rates for bleeding would anchor the timing of periprocedural OAC management. Based on early available data of background postprocedural bleed rates, it was suggested that the 2-day risk of MB in patients on chronic OAC without heparin bridging therapy was 0%-2% in low bleed risk procedures and 2%-4% in high bleed risk procedures.…”

“…25 Recent data from the PAUSE Trial with DOACs reveal that for low/ moderate bleed risk procedures the 30-day MB incidence was 0.9% (95% CI: 0-1.3), while that of high bleed risk procedures or surgeries was 2.48% (95% CI: 0-3.4). 24 For surgeries/procedures classified in the low/moderate bleedrisk category, a strategy of OAC interruption of two to three halflives preprocedure, which would enable some residual anticoagulant effect (ie 3 days off for warfarin, 1 day off for DOACs) and therapeutic-dose anticoagulant resumption within 1 day postprocedurally (for heparin bridging therapy with warfarin and for DOACs in general) would be associated with an acceptably low periprocedural bleeding risk. For procedures/surgeries in the high bleed-risk category, a strategy of OAC interruption of four to five half-lives preprocedure (ie, 5 days off for warfarin and 2 days off for DOACs), and resumption 2 to 3 days postprocedurally in the case of treatment-dose UFH or LMWH bridging therapy for warfarin and for DOACs in general would be associated with an acceptable periprocedural bleeding risk.…”

Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants

“…Permanent or temporary antithrombotic therapy is increasingly prescribed with the aging of the population in industrialized countries. Approximately 1 in 6 patients will require perioperative anticoagulation management including urgent surgery every year 1 . Furthermore, about 1% of the patients need treatment for acute DOAC‐associated bleeding 2 .…”