Comparison of 4-factor PCC reversal of apixaban and rivaroxaban versus warfarin for intracranial hemorrhage

Pasciolla, Stacy; Wojcik, Kevin; Kavi, Tapan; Green, Danielle; Shaikh, Hamza; Jankowitz, Brian; Igneri, Lauren

doi:10.1007/s11239-021-02613-1

Cited by 6 publications

(14 citation statements)

References 21 publications

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“…Thirty-six studies were included in the meta-analysis (eAppendix 1 in the Supplement ). Twenty-two studies with 967 participants evaluated 4F-PCC for reversal 8 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ; 17 studies with 525 participants evaluated AA 13 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ; and 5 studies with 340 participants evaluated idarucizumab, 12 , 53 , 54 , 55 , 56 consisting of a total of 1832 patients with ICH while receiving treatment with a DOAC. Eight studies had data on more than 1 agent.…”

Section: Resultsmentioning

confidence: 99%

“…Thirty-six studies were included in the meta-analysis (eAppendix 1 in the Supplement). Twenty-two studies with 967 participants evaluated 4F-PCC for reversal; 17 studies with 525 participants evaluated AA; and 5 studies with 340 participants evaluated idarucizumab, consisting of a total of 1832 patients with ICH while receiving treatment with a DOAC. Eight studies had data on more than 1 agent .…”

Section: Resultsmentioning

confidence: 99%

“…Several other smaller studies have shown the use of 4F-PCCs as a viable reversal option for DOAC-related ICH for anticoagulation reversal (reversal rates, 54.5%-94.7%) and safety (mortality rates, 4.7%-63.6%; thrombotic event rate, 0%-17.2%) . Albeit with significant heterogeneity, our meta-analysis found a combined proportion of anticoagulation reversed of 77%, a mortality rate of 26%, and a thromboembolic event rate of 8% (Figures 1-3).…”

Section: Discussionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

et al. 2022

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“…30 However, this may be due to time not being critical, as gastroenterology was among the 3 specialties to report the least incidence of life-threatening indications. 4F-PCC has been shown to be effective for treating VKA-associated ICH, 13,31 as well as DOAC-associated ICH, 32–35 and is recommended for the treatment of FXa inhibitor-associated ICH. 17,36 Guidelines for urgent or emergent cardiac surgery recommend 4F-PCC, when a specific reversal agent is not available, 37 despite limited clinical data available.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of the Real-World Utilization of 4-Factor Prothrombin Complex Concentrate and Plasma in Oral Anticoagulant-Associated Bleeding in US Hospitals

Refaai

Bajčić

McNeill

et al. 2023

Clin Appl Thromb Hemost

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Real-world utilization of 4-factor prothrombin complex concentrate (4F-PCC) and plasma for the management of oral anticoagulant (OAC)-associated bleeding in US trauma hospitals was described. This is amulticenter, retrospective chart review evaluating the use of 4F-PCC and plasma in OAC reversal across medical specialties. Physicians completed a survey and extracted data from 3 to 5 patient charts. Variables of interest included medical specialty, urgency, and bleed type. Two hundred and thirty-five physicians completed the survey, and 861 patient charts were included in the study. 4F-PCC was commonly used in life-threatening or emergent indications, whereas plasma was used in emergent and urgent indications. Plasma was used mostly for patients on warfarin (53% vs 47% 4F-PCC) and 4F-PCC for those on apixaban (82% vs 18% plasma) and rivaroxaban (77% vs 23% plasma). This retrospective analysis showed that 4F-PCC was predominantly used for OAC reversal despite available specific reversal agents for some of the OAC. Although it is not recommended by any reversal guidelines, plasma is still used for OAC reversal. Plasma should be avoided in the management of OAC-associated bleeding.

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“…Among retrospective studies, the majority (n ¼ 11) reported safety outcomes of 4F-PCC in patients requiring VKA reversal, [34][35][36][37][38][39][40][41][42][43][44] including three studies comparing fixed and standard variable dosing, [34][35][36] one study investigating VKA reversal for intracranial hemorrhage (ICH), 39 and one study comparing outcomes in patients with body weight over or under 100 kg. 40 Nine studies reporting the use of 4F-PCC for OAC (VKA or DOAC) reversal were retrieved, [45][46][47][48][49][50][51][52][53] including three studies examining 4F-PCC for reversal of VKA or DOAC-associated ICH 48,52,53 and one study comparing use of 4F-PCC for onlabel and off-label indications. 51 Two studies specifically investigated 4F-PCC as DOAC reversal therapy, 54,55 while three studies reported safety outcomes of 4F-PCC in nonanticoagulated patients.…”

Section: Safety Outcomes From Retrospective Studiesmentioning

confidence: 99%

Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review

Milling,

Voronov,

Schmidt

et al. 2024

Thromb Haemost

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Introduction Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra®/Beriplex® P/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data. Methods A retrospective analysis of postmarketing pharmacovigilance data of Kcentra®/Beriplex® P/N from February 1996 to April 2022 was performed and complemented by a review of clinical studies published between January 2012 and April 2022. Results A total of 2,321,443 standard infusions of Kcentra®/Beriplex® P/N were administered during the evaluation period. Adverse drug reactions (ADRs) were reported in 614 cases (∼1 per 3,781 standard infusions) and 233 of these cases (37.9%) experienced suspected TEEs related to 4F-PCC (∼1 per 9,963 standard infusions); most of these cases had pre-existing or concomitant conditions likely to be significant risk factors for thrombosis. TEE rates were similar when 4F-PCC was used on-label or off-label for direct oral anticoagulant-associated bleeding. Thirty-six cases (5.9%) reported hypersensitivity type reactions (∼1 per 64,485 standard infusions). No confirmed case of viral transmission related to 4F-PCC use was reported. The published literature also revealed a favorable safety profile of 4F-PCC. Conclusion Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC.

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Comparison of 4-factor PCC reversal of apixaban and rivaroxaban versus warfarin for intracranial hemorrhage

Cited by 6 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 Analysis of the Real-World Utilization of 4-Factor Prothrombin Complex Concentrate and Plasma in Oral Anticoagulant-Associated Bleeding in US Hospitals

Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review

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