Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel

Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding

“…the use of 4F-PCC for the reversal of fXa inhibitors; however, its exact place in therapy overall and in relation to andexanet alfa is discordant among these guidelines. 1,2,[9][10][11] Although andexanet alfa was specifically designed for reversal of fXa inhibitors, it has not seen widespread use because many institutions have not approved it due to a lack of robust evidence, including a comparator group in the available studies, questionable risk of thromboembolism, and the poor value proposition and cost-effectiveness of the therapy. 12,13 The range of recommendations for its use include the following: 4F-PCC as a first-line therapy for fXa inhibitor reversal 1,10,11 ; 4F-PCC as a first-line therapy as an alternative to discontinuation of fXa inhibitors alone (eg, meaning that perhaps no reversal agent would be appropriate) 2 ; and 4F-PCC as a second-line agent after andexanet alfa.…”

Reply to “Key Points to Consider When Evaluating Andexxa for Formulary Addition”

“…Although 4F-PCCs may constitute usual care in some hospitals, the data available to support its use are of a low quality of evidence, as the article authors noted. Given this low-quality evidence, several guidelines suggest the use of 4F-PCCs to reverse apixaban-or rivaroxabanassociated major bleeding, only if andexanet alfa is not available [3][4][5][6][7][8]. No prospective, randomized controlled studies have been conducted in bleeding patients to evaluate the efficacy of 4F-PCCs for reversal of anticoagulation with FXa inhibitors.…”

“…Lastly, in bleeding patients taking DOACs, PCC dosing ranges from ~ 10 to 160 units/kg with little standardization [6,15]. A recent study by Green et al [16] reported significantly increased mortality in patients with DOAC-associated bleeding treated with PCCs at doses > 25 units/kg-suggesting the possibility that PCCs may be more harmful than beneficial in this population without clear dosing trials.…”

“…Many guidelines were written before the availability of andexanet alfa and final ANNEXA-4 study results, and are currently under revision. More recent guidelines are placing andexanet alfa as a first-line agent in front of PCC [3][4][5][6][7][8].…”

Request for an Andexxa Value Analysis

“…However, some society guidelines, including the Anticoagulation Forum and the American College of Emergency Physicians, report that some guideline writers have conflicts of interest because they receive funding or are on the advisory board for Portola, the pharmaceutical company that manufactures Andexxa. 3,4 With the current (January 2020) cost of $22 000 for a package of four 200-mg vials of andexanet, treatment costs $27 500 for a low-dose course of therapy (400 mg intravenous [IV] bolus plus 480 mg over 120 minutes) and $49 500 for a high-dose course of therapy (800 mg IV bolus plus 960 mg over 120 minutes). Clinicians have questioned whether this therapy is cost-effective, particularly when compared with prothrombin complex concentrates (PCC), which cost approximately $3000 to $6000 for an average 70-kg patient (depending on the dosing strategy used, 25 or 50 U/kg).…”