SGEM#251: Nothing Compares to You…Because there was No Comparison Group

Date: April 5th, 2019 Reference: Connolly et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. NEJM 2019 Guest Skeptic: Dr. Ryan Radecki is an Emergency Physician at Kaiser Permanente NW, co-host of the Annals of Emergency Medicine podcast and Journal Club section editor. Case: You are caring for a 72-year-old man who comes in after having slipped on the ice.  A routine evaluation finds only minor bumps and bruises, including a rather nasty one on his occiput where he struck a step.  He reports he has been taking apixaban to prevent stroke in the context of atrial fibrillation, which you easily recognize as one of the modern oral anti-Factor Xa inhibitors.  You order a non-contrast CT to rule out hemorrhage. It demonstrates a 7mm subdural hematoma with 3mm of midline shift.  As you are reassessing your patient and treatment plan, the question presents itself – how should we reverse his anticoagulation? Background: More and more patients are being treated with direct oral anticoagulants (DOACs). This number will probably increase since the AHA/ACC/HRS 2019 updated guidelines for atrial fibrillation guidelines. It now contains the following recommendation: NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin in NOAC-eligible patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve). Level A One of the concerns clinicians had with DOACs was there was no way to reverse these new anti-coagulants when they were introduced. In contrast, protamine could be used for heparin and LMWH reversal and vitamin K, fresh frozen plasma and prothrombinase complex concentrate could be used to reverse coumadin (Hunt and Levi BMJ 2018). This changed in 2015 when the Food and Drug Administration (FDA) approved idarucizumab for the reversal of dabigatran. Dabigatran is a direct thrombin inhibitor. We covered the interim analysis of 90 patients included in a prospective cohort study by Pollack et al NEJM 2015 on SGEM#139. Our bottom line for that episode was that idarucizumab is here (USA) and probably works but its patient-oriented efficacy and safety are still pending. The full study cohort of 503 patients has since been published (Pollack et al NEJM 2017) and we are in the same place we were in 2015. Idarucizumab clearly and effectively removes dabigatran from circulation and this ought to be occasionally clinically useful. I would certainly exhaust all potential supportive and expectant management options first, as well as try to definitively confirm dabigatran as the culprit for abnormal hemostasis (EM Lit of Note). The FDA granted accelerated approval for andexanet alfa (Andexxa) in May of 2018. Andexxa is an antidote for factor Xa inhibitor like rivaroxaban, apixaban and edoxaban. It acts as a decoy and binds to the factor Xa inhibitors. The American College of Cardiology has published a fact sheet to provide some guidance for the use of anticoagulation reversal agents. Clinical Question: Should andexanet alfa be used to treat serious bleeding events in patients taking Factor Xa inhibitors? Reference: Connolly et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. NEJM 2019 Population: Adult patients presenting with an acute major bleed, and had received a DOAC (apixaban, rivaroxaban, or edoxaban) at any dose or enoxaparin at a dose of at least 1 mg per kilogram of body weight per day within the previous 18 hours. Acute Major Bleed: Bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic; bleeding associated with a decrease in the hemoglobin level of at least 2 g per deciliter or bleeding in a critical area or organ. Exclusions: There were a number of exclusions listed in supplemental material but the key ones were as follows: Planned surgery within 12hrs; ICH in a patient wit...