Efficacy and Safety of Andexanet Alfa for Bleeding Caused by Factor Xa Inhibitors: A Systematic Review and Meta-Analysis

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.

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey

“…Shrestha et al, 32 a systematic review and meta-analysis of 1245 studies published in 2021, concluded andexanet alfa reduced in-hospital mortality in patients who had bleeding attributed to factor Xa inhibitors compared to 4F-PCC. There was no statistical difference in thrombotic events.…”

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta‐analysis

“…1 Only two MAs specifically pooled comparative studies of andexanet alfa versus PCC products, and additional comparative studies have since been published. 1,14 Previous MAs also did not systematically evaluate the risk of bias within each included study and the impact of including studies with high risk of bias on the results, nor was appropriate caution applied when interpreting the results. 1,[7][8][9][10]14 The inclusion of studies at high risk of bias in a MA may distort the observed effect away from the true effect.…”

“…with rationales for the ratings. 1,14 The Shrestha 2021 MA included only three studies (Ammar 2021, Barra 2020, Coleman 2021). 14,28,29,31 The most recent systematic review by Chaudhury had a high risk of bias.…”

“…1,14 The Shrestha 2021 MA included only three studies (Ammar 2021, Barra 2020, Coleman 2021). 14,28,29,31 The most recent systematic review by Chaudhury had a high risk of bias. 28,29,[35][36][37][38][39][40][41][42]44,45 Twelve of the comparative studies assessed for hemostatic efficacy (Figure 3).…”

Spezifische Pharmakotherapie bei intrazerebralen Blutungen unter oraler Antikoagulation

“…Die Evidenzlage bezüglich thromboembolischer Komplikationen je nach dem Gegenmittel ist nicht eindeutig. Einige Studien konnten keine signifikanten Unterschiede zwischen dem Thromboembolierisiko nach Andexanet-alfa-und PPSB-Gabe finden [41,42]. In der Metaanalyse von Gómez-Outes et al waren Thromboembolien nach Andexanet-alfa-Gabe jedoch signifikant häufiger (10,7%) im Vergleich zum generellen Thromboembolierisiko nach allen 3 untersuchten Gegenmitteln (Andexanet alfa, Idarucizumab, PPSB; 4,6%) Dies beruht möglicherweise auf einem prothrombotischen Rebound-Effekt, da Andexanet alfa vorübergehend die Thrombinproduktion steigern kann [38].…”