Comparison of 4-factor prothrombin complex concentrate and andexanet alfa for reversal of apixaban and rivaroxaban in the setting of intracranial hemorrhage

Lipski, Michelle; Pasciolla, Stacy; Wojcik, Kevin; Jankowitz, Brian; Igneri, Lauren

doi:10.1007/s11239-022-02752-z

Cited by 12 publications

(13 citation statements)

References 19 publications

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“…In patients with ICH, in-hospital mortality occurred in 12.6% of patients in the Andexanet alfa group compared to 23.3% of patients in the 4F-PCC group, with an odds ratio of 0.55 (95% CI, 0.39-0.76), i.e., the probability of dying during hospitalization were 45% lower with Andexanet alfa compared to 4F-PCC. Other studies also point in the same direction, showing the superiority of AA over 4F-PCC in terms of mortality, such as the studies by Barra et al [16] and Costa et al [17], in which the number of deaths was reduced 3-fold and 2.5-fold, respectively, in patients receiving Andexanet alfa. It is important to emphasize that these deaths were due to the exacerbation of intracranial hemorrhage.…”

Section: Mortality and Thrombotic Eventsmentioning

confidence: 71%

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies

Ferreira,

Oldemburg,

Leitão Filho

et al. 2024

JCM

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Background/Objectives: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. Methods: PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)” guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. Results: In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. Conclusions: Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.

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Section: Mortality and Thrombotic Eventsmentioning

confidence: 71%

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies

Ferreira,

Oldemburg,

Leitão Filho

et al. 2024

JCM

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“…The recommendations against the use of andexanet alfa in patients with life-threatening bleeds other than intracranial haemorrhage were based on a meta-analysis [43] and small retrospective studies [16,17,44] because these studies did not demonstrate an advantage of prescribing andexanet alfa over 4F-PCC in this indication. Conversely, the use of 4F-PCC during bleeding in the context of anticoagulation with DOACs is based on few clinical data, and animal and in vitro or ex vivo studies as well as a lack of alternative treatment options [45][46][47][48][49][50][51][52][53].…”

Section: Methodological Limitations Of Available Evidence For Anticoa...mentioning

confidence: 99%

“…In a retrospective study analyzing the use of the health-system guideline, a comparable haemostatic efficacy was observed in patients receiving andexanet alfa and 4F-PCC, and a greater incidence of thromboembolic events was noted in patients receiving andexanet alfa than in those receiving 4F-PCC [16]. Another small retrospective study showed a comparable haemostatic efficacy and no difference in thromboembolic events between andexanet alfa and 4F-PCC in patients with intracranial haemorrhage [17]. In another study, andexanet alfa was associated with a lower rate of haematoma expansion in patients with atraumatic factor Xa inhibitor-related intracranial haemorrhage, but without translating into significantly improved clinical outcomes [18].…”

Section: Introductionmentioning

confidence: 97%

Recommendations for the use of andexanet alfa in the management of bleeding in patients on oral factor Xa inhibitors in Switzerland

Angelillo‐Scherrer¹,

Casini²,

Studt³

et al. 2023

Swiss Med Wkly

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Anticoagulants are essential in preventing and treating thrombosis. Unfortunately, their use is accompanied by an enhanced risk of bleeding. Since the introduction of direct oral anticoagulants (DOACs), the risk of major bleeding has been reduced but not eliminated. Major bleeding events related to the use of factor Xa inhibitors can be challenging to manage. In recent years, four-factor prothrombin complex concentrates have been used in patients with severe bleeding taking oral direct factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). Andexanet alfa (OndexxyaTM, AstraZeneca AG) is a specially designed recombinant version of human factor Xa that acts as a decoy receptor to reverse the effects of factor Xa inhibitors. Since 2 December 2020, andexanet alfa has been used in Switzerland for adult patients receiving apixaban or rivaroxaban when reversal of anticoagulation is required because of life-threatening or uncontrolled bleeding. However, the use of andexanet alfa remains a challenge owing to its cost, the reported thrombotic complications and the fact that its efficacy mainly relates to intracranial haemorrhage. Moreover, the use of nonspecific reversal agents together with andexanet alfa is controversial. The present recommendations on the use of andexanet alfa in the management of bleeding in patients on factor Xa inhibitors in Switzerland were developed by a group of Swiss experts from the Working Party Hemostasis of the Swiss Society of Hematology. These recommendations aim to provide support to clinicians in their decision-making in the management of patients with major bleeding receiving factor Xa inhibitors.

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“…We identified 18 studies for the review that fit the inclusion criteria and two systematic reviews (Figure 1). [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Study characteristics for the comparative studies and the systematic reviews are reported in Tables S3-S5. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Three studies used ANNEXA-4 data for their andexanet alfa arms (Cohen 2022, Costa 2022, Huttner 2022) with adjusted control groups.…”

Section: Articles Includedmentioning

confidence: 99%

“…[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Study characteristics for the comparative studies and the systematic reviews are reported in Tables S3-S5. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Three studies used ANNEXA-4 data for their andexanet alfa arms (Cohen 2022, Costa 2022, Huttner 2022) with adjusted control groups. 30,32,34 All three studies were included in our systematic review, and the risk of bias was assessed for each of these studies separately, but, as described above, only one study was used for each pooled analysis.…”

Section: Articles Includedmentioning

confidence: 99%

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

White,

Caroti,

Bessada

et al. 2024

Pharmacotherapy

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Previous meta‐analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)‐associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta‐analysis on the effectiveness of AA versus PCC products for FXaI‐associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn‐Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random‐effects meta‐analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in‐hospital mortality, 30‐day mortality, and thrombotic events. Low–moderate risk of bias studies were meta‐analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty‐eight percent of the studies (n = 5) had low–moderate risk and 72% (n = 13) had a high risk of bias. Studies with low–moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15–6.44); one study], lower in‐hospital mortality [OR 0.48 (95% CI: 0.38–0.61); three studies], and reduced 30‐day mortality [OR 0.49 (95% CI: 0.30–0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01–1.84); 12 studies] and reductions in 30‐day mortality [OR 0.53 (95% CI: 0.37–0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low–moderate, high, or combined risk of bias groups. The evidence from low–moderate quality real‐world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in‐hospital and 30‐day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30‐day mortality risk remain significantly better with AA versus PCC.

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Comparison of 4-factor prothrombin complex concentrate and andexanet alfa for reversal of apixaban and rivaroxaban in the setting of intracranial hemorrhage

Cited by 12 publications

References 19 publications

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies

Recommendations for the use of andexanet alfa in the management of bleeding in patients on oral factor Xa inhibitors in Switzerland

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

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