Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding
Abstract Objective Compare 30‐day mortality among patients receiving the specific reversal agent andexanet alfa versus replacement prothrombin complex concentrate (PCC) in the management of direct‐acting oral anticoagulant (DOAC)–related bleeds. Methods Two patient‐level datasets were used: ANNEXA‐4...
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| Language: | English |
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Elsevier
2022-04-01
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| Series: | Journal of the American College of Emergency Physicians Open |
| Online Access: | https://doi.org/10.1002/emp2.12655 |
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| author | Alexander T. Cohen Megan Lewis Augusta Connor Stuart J. Connolly Patrick Yue John Curnutte Raza Alikhan Peter MacCallum Joachim Tan Laura Green |
| author_facet | Alexander T. Cohen Megan Lewis Augusta Connor Stuart J. Connolly Patrick Yue John Curnutte Raza Alikhan Peter MacCallum Joachim Tan Laura Green |
| author_sort | Alexander T. Cohen |
| collection | DOAJ |
| description | Abstract Objective Compare 30‐day mortality among patients receiving the specific reversal agent andexanet alfa versus replacement prothrombin complex concentrate (PCC) in the management of direct‐acting oral anticoagulant (DOAC)–related bleeds. Methods Two patient‐level datasets were used: ANNEXA‐4, a prospective, single‐arm trial of patients taking apixaban or rivaroxaban who received andexanet alfa and ORANGE, a prospective, observational study of anticoagulated patients in UK hospitals, some of whom received PCC. Patients were propensity score matched based on demographic and clinical characteristics. Subgroup analyses were performed by bleed type (intracranial hemorrhage [ICH], gastrointestinal [GI], other). Relative risk (RR) of all‐cause 30‐day mortality was calculated. Results 322 ANNEXA‐4 patients treated with andexanet alfa (mean age = 77.7 years; 64.9% ICH) were matched with 88 ORANGE patients treated with PCC (mean age = 74.9 years, 67.1% ICH). Adjusted 30‐day mortality for patients treated with andexanet alfa (14.6%) was lower than patients treated with PCC (34.1%; RR, 0.43; 95% CI, 0.29–0.63). In the ICH subgroup, patients treated with andexanet alfa had lower mortality (15.3%) than patients treated with PCC (48.9%; RR, 0.31; 95% CI, 0.20–0.48). Mortality risk was lowest for patients in the GI subgroup but did not differ significantly by treatment (12.2% for andexanet alfa vs 25.0% for PCC; RR, 0.49; 95% CI, 0.21–1.16). Conclusions In this propensity score–matched comparison across 2 independent datasets, adjusted 30‐day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC. This indirect comparison was limited in that it could not account for several highly predictive variables including GCS score, hematoma volume, and expected survival. Further research is warranted to confirm the mortality differences between reversal/replacement agents for DOAC‐related bleeding. |
| format | Article |
| id | doaj-art-9a49da103d534d07a8f7b929a8e370b3 |
| institution | OA Journals |
| issn | 2688-1152 |
| language | English |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
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| series | Journal of the American College of Emergency Physicians Open |
| spelling | doaj-art-9a49da103d534d07a8f7b929a8e370b32025-08-20T02:00:38ZengElsevierJournal of the American College of Emergency Physicians Open2688-11522022-04-0132n/an/a10.1002/emp2.12655Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleedingAlexander T. Cohen0Megan Lewis1Augusta Connor2Stuart J. Connolly3Patrick Yue4John Curnutte5Raza Alikhan6Peter MacCallum7Joachim Tan8Laura Green9Department of Haematological Medicine Guy's and St Thomas’ Hospitals London UKHEOR and Access FIECON Ltd St Albans UKHEOR and Access FIECON Ltd St Albans UKPopulation Health Research Institute McMaster University Hamilton Ontario CanadaPortola Pharmaceuticals, Inc. now Alexion Pharmaceuticals, Inc. South San Francisco California USAPortola Pharmaceuticals, Inc. now Alexion Pharmaceuticals, Inc. South San Francisco California USAUniversity Hospital of Wales, Cardiff and Vale University Health Board Cardiff UKHaemostasis and Transfusion Barts Health NHS Trust London UKPopulation Health Research Institute St George's, University of London London UKHaemostasis and Transfusion Barts Health NHS Trust London UKAbstract Objective Compare 30‐day mortality among patients receiving the specific reversal agent andexanet alfa versus replacement prothrombin complex concentrate (PCC) in the management of direct‐acting oral anticoagulant (DOAC)–related bleeds. Methods Two patient‐level datasets were used: ANNEXA‐4, a prospective, single‐arm trial of patients taking apixaban or rivaroxaban who received andexanet alfa and ORANGE, a prospective, observational study of anticoagulated patients in UK hospitals, some of whom received PCC. Patients were propensity score matched based on demographic and clinical characteristics. Subgroup analyses were performed by bleed type (intracranial hemorrhage [ICH], gastrointestinal [GI], other). Relative risk (RR) of all‐cause 30‐day mortality was calculated. Results 322 ANNEXA‐4 patients treated with andexanet alfa (mean age = 77.7 years; 64.9% ICH) were matched with 88 ORANGE patients treated with PCC (mean age = 74.9 years, 67.1% ICH). Adjusted 30‐day mortality for patients treated with andexanet alfa (14.6%) was lower than patients treated with PCC (34.1%; RR, 0.43; 95% CI, 0.29–0.63). In the ICH subgroup, patients treated with andexanet alfa had lower mortality (15.3%) than patients treated with PCC (48.9%; RR, 0.31; 95% CI, 0.20–0.48). Mortality risk was lowest for patients in the GI subgroup but did not differ significantly by treatment (12.2% for andexanet alfa vs 25.0% for PCC; RR, 0.49; 95% CI, 0.21–1.16). Conclusions In this propensity score–matched comparison across 2 independent datasets, adjusted 30‐day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC. This indirect comparison was limited in that it could not account for several highly predictive variables including GCS score, hematoma volume, and expected survival. Further research is warranted to confirm the mortality differences between reversal/replacement agents for DOAC‐related bleeding.https://doi.org/10.1002/emp2.12655 |
| spellingShingle | Alexander T. Cohen Megan Lewis Augusta Connor Stuart J. Connolly Patrick Yue John Curnutte Raza Alikhan Peter MacCallum Joachim Tan Laura Green Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding Journal of the American College of Emergency Physicians Open |
| title | Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding |
| title_full | Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding |
| title_fullStr | Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding |
| title_full_unstemmed | Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding |
| title_short | Thirty‐day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life‐threatening direct oral anticoagulant‐related bleeding |
| title_sort | thirty day mortality with andexanet alfa compared with prothrombin complex concentrate therapy for life threatening direct oral anticoagulant related bleeding |
| url | https://doi.org/10.1002/emp2.12655 |
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