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Background: Factor Xa inhibitors have become increasingly popular in the treatment and prevention of thrombotic events, but the lack of specific reversal agents in the event of life-threatening or uncontrolled bleeding may limit their use. Andexanet alfa is a new Food and Drug Administration–approved reversal agent which rapidly reduces anti–factor Xa activity, thereby reversing the anticoagulation effects of factor Xa inhibitors.
Study design: A prospective, open-label, single-group cohort study.
Setting: An industry-sponsored, multicenter study.
Synopsis: The study evaluated 352 adult patients who had acute major bleeding (such as intracranial hemorrhage [64%] or GI bleeding [26%] within 18 hours after administration of a factor Xa inhibitor, including apixaban, rivaroxaban, or edoxaban). Efficacy was assessed in 254 patients who met criteria for severe bleeding and elevated baseline anti–factor Xa activity. Patients were administered a bolus dose of andexanet alfa followed by a 2-hour infusion. The median anti–factor Xa activity reduced by 92% each among patients receiving apixaban or rivaroxaban. The majority (82%) of evaluable patients achieved excellent or good hemostasis at 12 hours after andexanet alfa administration, which compares favorably with the hemostatic efficacy of 72% observed with prothrombin complex concentrate used to reverse anticoagulation in patients treated with vitamin K antagonists. Of patients in the study, 10% experienced a thrombotic event during the 30-day follow-up period, and 14% died.
Limitations of the study include lack of a control group and absence of a significant relationship between a reduction in anti–factor Xa activity and hemostasis. The sponsor is planning to conduct a randomized trial with FDA guidance in the near future.
Bottom line: Andexanet alfa is an FDA-approved agent and appears effective in achieving hemostasis in patients with a factor Xa inhibitor–associated major acute bleeding.
Citation: Connolly SJ et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Eng J Med. 2019 Feb 7. doi: 10.1056/NEJMoa1814051.
Dr. Vedamurthy is a hospitalist at Massachusetts General Hospital.
Background: Factor Xa inhibitors have become increasingly popular in the treatment and prevention of thrombotic events, but the lack of specific reversal agents in the event of life-threatening or uncontrolled bleeding may limit their use. Andexanet alfa is a new Food and Drug Administration–approved reversal agent which rapidly reduces anti–factor Xa activity, thereby reversing the anticoagulation effects of factor Xa inhibitors.
Study design: A prospective, open-label, single-group cohort study.
Setting: An industry-sponsored, multicenter study.
Synopsis: The study evaluated 352 adult patients who had acute major bleeding (such as intracranial hemorrhage [64%] or GI bleeding [26%] within 18 hours after administration of a factor Xa inhibitor, including apixaban, rivaroxaban, or edoxaban). Efficacy was assessed in 254 patients who met criteria for severe bleeding and elevated baseline anti–factor Xa activity. Patients were administered a bolus dose of andexanet alfa followed by a 2-hour infusion. The median anti–factor Xa activity reduced by 92% each among patients receiving apixaban or rivaroxaban. The majority (82%) of evaluable patients achieved excellent or good hemostasis at 12 hours after andexanet alfa administration, which compares favorably with the hemostatic efficacy of 72% observed with prothrombin complex concentrate used to reverse anticoagulation in patients treated with vitamin K antagonists. Of patients in the study, 10% experienced a thrombotic event during the 30-day follow-up period, and 14% died.
Limitations of the study include lack of a control group and absence of a significant relationship between a reduction in anti–factor Xa activity and hemostasis. The sponsor is planning to conduct a randomized trial with FDA guidance in the near future.
Bottom line: Andexanet alfa is an FDA-approved agent and appears effective in achieving hemostasis in patients with a factor Xa inhibitor–associated major acute bleeding.
Citation: Connolly SJ et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Eng J Med. 2019 Feb 7. doi: 10.1056/NEJMoa1814051.
Dr. Vedamurthy is a hospitalist at Massachusetts General Hospital.
Background: Factor Xa inhibitors have become increasingly popular in the treatment and prevention of thrombotic events, but the lack of specific reversal agents in the event of life-threatening or uncontrolled bleeding may limit their use. Andexanet alfa is a new Food and Drug Administration–approved reversal agent which rapidly reduces anti–factor Xa activity, thereby reversing the anticoagulation effects of factor Xa inhibitors.
Study design: A prospective, open-label, single-group cohort study.
Setting: An industry-sponsored, multicenter study.
Synopsis: The study evaluated 352 adult patients who had acute major bleeding (such as intracranial hemorrhage [64%] or GI bleeding [26%] within 18 hours after administration of a factor Xa inhibitor, including apixaban, rivaroxaban, or edoxaban). Efficacy was assessed in 254 patients who met criteria for severe bleeding and elevated baseline anti–factor Xa activity. Patients were administered a bolus dose of andexanet alfa followed by a 2-hour infusion. The median anti–factor Xa activity reduced by 92% each among patients receiving apixaban or rivaroxaban. The majority (82%) of evaluable patients achieved excellent or good hemostasis at 12 hours after andexanet alfa administration, which compares favorably with the hemostatic efficacy of 72% observed with prothrombin complex concentrate used to reverse anticoagulation in patients treated with vitamin K antagonists. Of patients in the study, 10% experienced a thrombotic event during the 30-day follow-up period, and 14% died.
Limitations of the study include lack of a control group and absence of a significant relationship between a reduction in anti–factor Xa activity and hemostasis. The sponsor is planning to conduct a randomized trial with FDA guidance in the near future.
Bottom line: Andexanet alfa is an FDA-approved agent and appears effective in achieving hemostasis in patients with a factor Xa inhibitor–associated major acute bleeding.
Citation: Connolly SJ et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Eng J Med. 2019 Feb 7. doi: 10.1056/NEJMoa1814051.
Dr. Vedamurthy is a hospitalist at Massachusetts General Hospital.