OC 71.2 - PAUSE-2 Randomized Pilot Trial to Compare Two Strategies (PAUSE vs. ASRA) for Perioperative DOAC Management

Background: There is uncertainty about how to manage patients taking a direct oral anticoagulant (DOAC) who need a high-bleed-risk surgery/neuraxial anesthesia. There are two possible strategies: (i) PAUSE management, derived from the PAUSE study, requires DOAC interruption for 2 days before and after a high-bleed-risk surgery/neuraxial procedure, without heparin bridging or DOAC level testing; (ii) ASRA management, derived from the American Society of Regional Anesthesia guidelines, requires DOAC interruption for 3-5 days, resumption within 24 hours post-op and heparin bridging and DOAC levels in selected patients.

Aims: This pilot study aims to assess feasibility of a larger RCT and to identify possible safety signal concerns in either strategy.

Methods: PAUSE-2 pilot is an open-label, randomized controlled trial (RCT) that compares the PAUSE vs. ASRA strategy for perioperative DOAC management in patients with atrial fibrillation needing a high-bleed-risk surgery/neuraxial anesthesia. We hypothesize that PAUSE management will be as safe as ASRA for the outcomes of major bleeding (2.5% both arms, 2% non-inferiority [NI] margin) and stroke/systemic embolism (0.5% both arms, 1% NI margin). A secondary outcome is residual DOAC levels, measured just before surgery. Patients are followed from randomization (3-5 days pre-surgery) until 30 days post-surgery. PAUSE-2 was approved by local research ethics boards; 80% of eligible patients consented to participate.

Results: As of January 28, 2022, 90 recruited patients from 3 clinical sites completed the 30-day follow-up. The patient/surgery characteristics are shown in Table 1. In a blinded analysis of all patients, there was no stroke/systemic embolism, major bleeding or deaths. One patient had a pulmonary embolism. Results of residual DOAC levels are ongoing, to be disclosed at the time of public presentation.

Conclusion(s): The PAUSE-2 pilot RCT demonstrates feasibility to conduct a large, adequately-powered trial. It successfully randomized patients to two perioperative DOAC management strategies, and does not appear to have safety signal concerns.