Abstract
Direct oral anticoagulants (DOAC) including factor Xa inhibitors are associated with bleeding events which can lead to severe morbidity and mortality. Reversal agents like andexanet alfa (AA) and 4F-PCC (Four-factor prothrombin concentrate complex) are available for treating bleeding that occurs with DOAC therapy but a comparison on their efficacy is lacking. In this study, we analyzed the efficacy and safety of patients treated with andexanet alfa for bleeding events from DOAC. Databases were searched for relevant studies where AA was used to determine efficacy and safety in bleeding patients who were on factor Xa inhibitors. Published papers were screened independently by two authors. RevMan 5.4 (The Cochrane Collaboration, 2020) was used for data synthesis. Odds ratio (OR) and mean difference (MD) was used to estimate the outcome with a 95% confidence interval (CI). Among 1245 studies were identified after a thorough database search and three studies were included for analysis. AA resulted in lower odds of mortality compared to 4F- PCC (OR, 0.37; 95% CI, 0.20-0.71) among patients with intracerebral hemorrhage. There was no difference in thrombotic events between patients receiving AA and 4F-PCC (OR, 2.40; 95% CI, 0.36-15.84). No differences in length of hospital stay and intensive care unit (ICU) stay were seen between patients receiving AA and 4F-PCC. In conclusion, andexanet alfa reduced in-hospital mortality in patients who had bleeding due to factor Xa inhibitors compared to 4F-PCC. However, there were no differences in thrombotic events, length of ICU, and hospital stay between patients treated with AA and 4F-PCC.
Highlights
BackgroundDirect oral anticoagulants (DOAC) have been increasingly used in patients for the prevention of systemic embolization in atrial fibrillation as well as treatment and prevention of deep vein thrombosis (DVT) and venous thromboembolism (VTE)
The major finding of our study was that andexanet alfa decreased mortality in patients who had intracerebral bleeding due to factor Xa inhibitors compared to 4 factor-prothrombin concentrate complex (4F-Prothrombin complex concentrates (PCCs))
We found no difference in the incidence of thrombotic events caused by AA in comparison to 4F-PCC for the reversal of bleeding caused by factor Xa inhibitor
Summary
BackgroundDirect oral anticoagulants (DOAC) have been increasingly used in patients for the prevention of systemic embolization in atrial fibrillation as well as treatment and prevention of deep vein thrombosis (DVT) and venous thromboembolism (VTE). Factor Xa inhibitors reduce fatal and intracranial hemorrhage compared with vitamin K antagonists [7,8]. Fatal bleeding has been reported with oral factor Xa inhibitor use [8,9]. Before the introduction of andexanet alfa (AA), off-label use of 4 factor-prothrombin concentrate complex (4F-PCC) was advised and was used in the situation of life-threatening bleeding [10]. In May 2018, AA received FDA approval for use in patients treated with rivaroxaban and apixaban in the setting of life-threatening or uncontrolled bleeding following ANNEXA-A and ANNEXA-R trials in healthy participants [12,13]. A multicenter, prospective, open-label, single-group study ANNEXA-4 was done in bleeding patients following FDA approval, which showed the drug's good efficacy and safety profile [15]. We have conducted this systematic review and meta-analysis to analyze the effectiveness and safety profile of AA in bleeding caused by factor Xa inhibitors
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