Real-world Management of Oral Factor Xa inhibitor-related Bleeds With Reversal Or Replacement Agents Including Andexanet Alfa and four-factor Prothrombin Complex Concentrate: A Multicenter Study

Coleman, Craig I; Dobesh, Paul P.; Danese, Sherry; Ulloa, Julie; Lovelace, Belinda

doi:10.2217/fca-2020-0073

Cited by 36 publications

(49 citation statements)

References 21 publications

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“…After the exclusion of these 2 studies, the data on the comparison of 4F-PCC and AA were derived from 8 retrospective studies. [35][36][37][39][40][41][42]44 We found that 4F-PCC had a comparable proportion of successful…”

Section: Subanalysismentioning

confidence: 60%

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

et al. 2022

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ImportanceDirect oral anticoagulant (DOAC)–associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and RelevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

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Section: Subanalysismentioning

confidence: 60%

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

et al. 2022

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“…Two other retrospective analyses have associated a decreased incidence of mortality with andexanet alfa compared to 4F-PCC. 31,32 However, a metaanalysis associated andexanet alfa with a nonsignificantly increased hospital mortality yet a numerically lower 30-day mortality. 38 A randomized prospective study is needed to further examine these associations.…”

Section: Discussionmentioning

confidence: 99%

“…5,29,30 Irrespective of these recommendations there is currently limited evidence comparing the 2 agents. 15,[31][32][33] Therefore, the aim of this retrospective cohort is to compare hemostatic efficacy and safety outcomes between andexanet alfa and 4F-PCC for reversal of FXa-inhibitor-related bleeding.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Comparison of Andexanet Alfa and 4-Factor Prothrombin Complex for Reversal of Factor Xa-Inhibitor Related Bleeding

Stevens

Trujillo

Kiser

et al. 2021

Clin Appl Thromb Hemost

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The aim of this retrospective study was to compare andexanet alfa and 4-factor prothrombin complex (4F-PCC) for reversal of factor Xa (FXa)-inhibitor bleeding. Patients that received andexanet alfa for reversal were included. An equivalent number of patients administered 4F-PCC for FXa-inhibitor bleeding were randomly selected as historical controls. The primary outcome was effective hemostasis achievement within 12 h, defined using ANNEXA-4 criteria. Thromboembolic events and mortality within 30 days were also evaluated. A total of 32 patients were included. Baseline characteristics were not statistically different between andexanet alfa (n = 16) and 4F-PCC (n = 16). Intracranial bleeding was the primary reversal indication in 43.8% versus 62.5% of patients, respectively. Effective hemostasis was reached in 75.0% of andexanet alfa patients compared to 62.5% of 4F-PCC patients ( P = .70). Thromboembolic events occurred in 4 (25.0%) patients and 3 (18.8%) patients, respectively ( P = .99). Mortality incidence was 12.5% and 31.3%, respectively ( P = .39). Andexanet alfa and 4F-PCC attained hemostasis in a majority of patients. A high, but a similar rate of thromboembolic events was seen with both treatments. Prospective studies are needed to elucidate comparative risks and benefits of the 2 agents.

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“…Culbreth et al did studies also done by Brown et al and two studies in 2018, and 2019 had zero incidences of thrombotic events [ 20 , 22 , 23 ]. A retrospective study done by Coleman et al did not include the incidence of thrombotic events [ 19 ]. The most common thrombotic event reported was DVT; 19 out of 48 patients with thromboembolic events had DVT.…”

Section: Reviewmentioning

confidence: 99%

“…The Ammar et al study used different values for hematoma expansion, the Culbreth et al 2018 study reported repeat CT as stable or worsening while the Culbreth et al 2019 study which included patients requiring emergent surgery reported hemostatic effectiveness as per surgeon [ 17 , 22 , 23 ]. Coleman et al did not study hemostatic efficacy while Brown et al evaluated hemostatic efficacy in ICH and surgery requiring patients as hematoma expansion if there was >20% increase in pre-treatment hematoma volume or hematoma diameter [ 19 , 20 ]. ANNEXA-4 trial and the Steven et al study evaluated hemostatic efficacy by measuring anti-factor Xa activity, at end of 12 hours while 24 hours was used as the time frame in a study by Barra et al and Nederpelt et al [ 18 , 25 ].…”

Section: Reviewmentioning

confidence: 99%

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

Shrestha¹,

Budhathoki²,

Adhikari³

et al. 2021

Cureus

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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.

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Real-world Management of Oral Factor Xa inhibitor-related Bleeds With Reversal Or Replacement Agents Including Andexanet Alfa and four-factor Prothrombin Complex Concentrate: A Multicenter Study

Cited by 36 publications

References 21 publications

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

Retrospective Comparison of Andexanet Alfa and 4-Factor Prothrombin Complex for Reversal of Factor Xa-Inhibitor Related Bleeding

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

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