News > Medscape Medical News > Conference News > ISC 2019 ANNEXA-4 Published: Anti-Factor Xa Antidote Stops Major Bleeding Deborah Brauser February 15, 2019 previously released, the full study report was published online February 7 in the New England Journal of Medicine to coincide with its presentation here at the International Stroke Conference (ISC) 2019. The nonrandomized, open-label study included more than 300 patients with acute major bleeding associated with the use of factor Xa inhibitors. Among patients who had earlier received either apixaban (Eliquis, Bristol-Myers Squibb) or rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals), those who received an andexanet bolus showed a 92% reduction from baseline in anti–factor Xa activity, thereby meeting the co-primary efficacy outcome. Among the 249 patients assessed for hemostatic efficacy, 82% showed excellent or good clinical hemostasis 12 hours after an andexanet infusion — meeting the second co-primary outcome. "Reductions in anti–factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage," the investigators report. Safety results showed that 10% of the participants experienced a thrombotic event within 30 days and that 14% died. Dr Truman Milling Jr "There's now a reversal agent for all the anticoagulants," senior author Truman J. Milling Jr, MD, associate professor in the Department of Neurology and the Department of Surgery and Perioperative Care at the Dell Medical School at the University of Texas at Austin, told Medscape Medical News. "For the practicing emergency physician who deals with bleeding pretty regularly and has seen bad cases of anticoagulant-associated bleeding, that's a comfort," said Milling, who is also from the Seton Dell Medical School Stroke Institute. FDA-Approved Reversal Agent Andexanet alfa, a modified and recombinant form of factor Xa, was designed to "rapidly neutralize the anticoagulant effects" of factor Xa inhibitors at times of acute bleeding, the investigators note. These types of inhibitors "have a favorable benefit-risk profile for the treatment and prevention of thrombotic events but may cause or worsen acute major bleeding, with substantial morbidity and mortality," they add. As reported by Medscape Medical News, the US Food and Drug Administration (FDA) approved the agent in May 2018 under its Accelerated Approval Program. It's indicated to reverse the inhibitors' anticoagulation effects as needed because of life-threatening or uncontrolled bleeding. The agent is currently under review by the European Medicines Agency.
N Engl J Med. 2018 Sep 20;379(12):1118-1127. doi: 10.1056/NEJMoa1805090. Epub 2018 Aug 26. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Collaborators (697) Abstract BACKGROUND: Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS: In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS: Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .). Comment in In at-risk medical patients, rivaroxaban after discharge did not reduce symptomatic or fatal VTE at 45 days. [Ann Intern Med. 2018] Thromboprophylaxis after Hospitalization for Medical Illness. [N Engl J Med. 2018] DOAK nach der Klinik verhindern keine VTE. [MMW Fortschr Med. 2019] PMID: 30145946 DOI: 10.1056/NEJMoa1805090
