An Evaluation of Andexanet Alfa v. Standard of Care for Reversal of Doac-Induced Intracranial Hemorrhage - a Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Background Direct oral anticoagulants (DOACs) are reversible factor X inhibitors used to treat and prevent thrombotic complications such as venous thromboembolism and stroke in patients with atrial fibrillation. While offering benefits over traditional anticoagulants, they continue to present the risk of bleeding events, including intracranial hemorrhage (ICH). A recombinant form of factor Xa, Andexanet alfa, is available in some jurisdictions to reverse DOAC effects in patients with life-threatening or uncontrolled bleeding. Previous studies, including a recently published randomised controlled trial (RCT) have observed improvements in hemostatic efficacy and reductions in anti-factor Xa activity compared with “standard of care”. However, pooled efficacy, thrombotic events, and the impact on 30-day mortality reduction is unclear. Objective We performed a systematic review and meta-analysis to determine hemostatic efficacy, thrombotic complications, and mortality in ICH patients receiving Andexanet alfa compared to standard of care. Methods We searched Ovid Medline, EMBASE, CINAHL, and the reference lists of eligible publications for relevant studies published until June 7th, 2024 using a librarian-approved search strategy. Studies were included if they were a prospective or retrospective cohort study or randomized controlled trial (RCT) enrolling more than 15 patients that directly compared Andexanet alfa to standard of care options, as defined by the study, in the context of DOAC-induced ICH. The primary efficacy outcome was hemostatic efficacy, as defined by individual studies. Primary safety outcomes included rates of thrombotic complications, both venous and arterial, and mortality. Secondary outcomes included subgroup analyses of different standard-of-care options. The Review Manager (RevMan) tool, version 7.14.1, was used to pool outcome rates and calculate Mantel-Haenszel (M-H) risk ratios using a random effects model. Results A total of 2423 records were screened, with a total of 22 studies (n = 4330 patients) included in this analysis. Twenty (90.9%) studies were retrospective cohort studies, one (4.5%) was a randomized controlled trial, and one (4.5%) was an analysis of two prospective cohort studies. Eighteen (81.8%) studies predominately or exclusively used 4-factor prothrombin complex concentrate (4F-PCC) as the standard of care, 4 (18.2%) studies used 3-factor and activated PCC, one examined fresh frozen plasma (FFP), and one examined tranexamic acid. The two most commonly documented DOACs were apixaban (n = 1072) and rivaroxaban (n = 716). The most common indication for DOAC use was atrial fibrillation (n = 1874), followed by VTE (n = 239). Of the studies examining hemostatic efficacy, the majority (n = 9, 64.3%) used the ANNEXA-4 criteria for hemostasis, followed by ISTH criteria (n = 3, 21.4%). Fourteen studies reported hemostatic efficacy, with a pooled risk ratio of 1.1 (95% CI 1.03-1.20, p = 0.005, I2 = 18%) favouring Andexanet alfa. Thirteen studies reported thrombotic events, with a pooled risk ratio of 1.22 (95% CI 0.86-1.74, p = 0.26, I2 = 0%). Finally, 13 studies examined mortality, with a pooled risk ratio of 0.81 (95% CI 0.63-1.05, p = 0.26, I2 = 42%). Subgroup analyses comparing Andexanet alfa to 4F-PCC found similar results across hemostatic efficacy and thrombotic complications but noted a significant mortality risk reduction in favour of Andexanet alfa (RR 0.76, 95% CI: 0.58-0.99, p=0.04, I2 = 38%). Heterogeneity was low for both hemostatic efficacy and thrombotic complications and moderate for mortality. Conclusions Our meta-analysis found improved hemostatic efficacy with Andexanet alfa compared to standard-of-care, with no effect on thrombotic complications and mortality rates. This suggests that Andexanet alfa is a favourable treatment option for hemostasis in patients experiencing life-threatening ICH.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.022 | 0.043 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".