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. 2021 May 24;5(4):e12518.
doi: 10.1002/rth2.12518. eCollection 2021 May.

A meta-analysis of andexanet alfa and prothrombin complex concentrate in the treatment of factor Xa inhibitor-related major bleeding

Tessa Jaspers  1 , Kimberly Shudofsky  2 , Menno V Huisman  3 , Karina Meijer  4 , Nakisa Khorsand  5
Affiliations

A meta-analysis of andexanet alfa and prothrombin complex concentrate in the treatment of factor Xa inhibitor-related major bleeding

Tessa Jaspers et al. Res Pract Thromb Haemost. .

Abstract

Background: Andexanet alfa (andexanet) and prothrombin complex concentrate (PCC) are both reversal agents for major bleeding in patients using factor Xa inhibitors (FXaIs). Our aim was to evaluate the current evidence for the effectiveness and safety of andexanet and PCC in a systematic review and meta-analysis.

Objectives: Primary objective was hemostatic effectiveness. Secondary objectives were thromboembolic event rate and mortality.

Methods: A systematic review was performed in PubMed and Embase. Studies describing the effectiveness and/or safety of PCC or andexanet in patients with major bleeding using FXaIs were included. Meta-analysis was performed using a random-effects model.

Results: Seventeen PCC studies, 3 andexanet studies, and 1 study describing PCC and andexanet were included, comprising 1428 PCC-treated and 396 andexanet-treated patients. None of the included studies had control groups, hampering a pooled meta-analysis to compare the two reversal agents. Separate analyses for andexanet and PCC were performed. In subgroup analysis, the pooled proportion of patients with effective hemostasis in studies that used Annexa-4 criteria demonstrated a hemostatic effectiveness of 0.85 (95% confidence interval [CI], 0.80-0.90) in PCC and 0.82 (95% CI, 0.78-0.87) in andexanet studies. The pooled proportion of patients with thromboembolic events was 0.03 (95% CI, 0.02-0.04) in PCC and 0.11 (95% CI, 0.04-0.18) in andexanet studies.

Conclusion: Based on the available evidence with low certainty from observational studies, PCC and andexanet demonstrated a similar, effective hemostasis in the treatment of major bleeding in patients using FXaIs. Compared to PCC, the thromboembolic event rate appeared higher in andexanet-treated patients.

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Figures

FIGURE 1
FIGURE 1
Study selection. 1 Reason for exclusion: updates/reviews: 132, editorial/expert opinion: 50, ex vivo/in vitro study: 44, perioperative usage: 35, no major bleeding in FXa‐I users: 30, no PCC or and exanet used: 25, study in healthy volunteers: 19, case reports: 18, guideline: 18, study in animals: 12, cost‐efficacy analysis: 4, erratum: 2, survey: 1, preliminary results: 1. 2 Reason for exclusion: review: 26, no major bleeding in FXa‐I users: 7, ex vivo/in vitro study: 3, healthy volunteers: 2, no relevant outcome measures: 2, preliminary results: 1, no PCC or andexanet used: 1, ≤10 patients: 1, survey: 1. 3 Reason for exclusion: Outcome measures could not be extracted for the study population ‘major bleeding while using FXa‐I, treated with andexanet or PCC’: 27, review: 17, editorial/expert opinion: 11, case reports: 6, ≤10 patients: 5, no major bleeding in FXa‐I users: 5, perioperative usage: 2, in vitro study: 1
FIGURE 2
FIGURE 2
Forest plots of the pooled outcome proportions. aPCC, activated prothrombin complex concentrate; PCC, prothrombin complex concentrate
See this image and copyright information in PMC

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