Isabelle Mahé, Marc Carrier, Didier Mayeur, Jean Chidiac, Eric Vicaut, Nicolas Falvo, Olivier Sanchez, Claire Grange, Manuel Monreal, Juan J López-Núñez, Remedios Otero-Candelera, Grégoire Le Gal, Erik Yeo, Marc Righini, Helia Robert-Ebadi, Menno V Huisman, Frederikus A Klok, Peter Westerweel, Giancarlo Agnelli, Cecilia Becattini, Aristotelis Bamias, Kostas Syrigos, Sebastian Szmit, Adam Torbicki, Peter Verhamme, Anthony Maraveyas, Alexander T Cohen, Cihan Ay, Céline Chapelle, Guy Meyer, Francis Couturaud, Patrick Mismetti, Philippe Girard, Laurent Bertoletti, Silvy Laporte
{"title":"Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism.","authors":"Isabelle Mahé, Marc Carrier, Didier Mayeur, Jean Chidiac, Eric Vicaut, Nicolas Falvo, Olivier Sanchez, Claire Grange, Manuel Monreal, Juan J López-Núñez, Remedios Otero-Candelera, Grégoire Le Gal, Erik Yeo, Marc Righini, Helia Robert-Ebadi, Menno V Huisman, Frederikus A Klok, Peter Westerweel, Giancarlo Agnelli, Cecilia Becattini, Aristotelis Bamias, Kostas Syrigos, Sebastian Szmit, Adam Torbicki, Peter Verhamme, Anthony Maraveyas, Alexander T Cohen, Cihan Ay, Céline Chapelle, Guy Meyer, Francis Couturaud, Patrick Mismetti, Philippe Girard, Laurent Bertoletti, Silvy Laporte","doi":"10.1056/NEJMoa2416112","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In patients with active cancer and venous thromboembolism, whether extended treatment with a reduced dose of an oral anticoagulant is effective in preventing recurrent thromboembolic events and decreasing bleeding is unclear.</p><p><strong>Methods: </strong>We conducted a randomized, double-blind, noninferiority trial with blinded central outcome adjudication. Consecutive patients with active cancer and proximal deep-vein thrombosis or pulmonary embolism who had completed at least 6 months of anticoagulant therapy were randomly assigned in a 1:1 ratio to receive oral apixaban at a reduced (2.5 mg) or full (5.0 mg) dose twice daily for 12 months. The primary outcome was centrally adjudicated fatal or nonfatal recurrent venous thromboembolism, assessed in a noninferiority analysis (margin of 2.00 for the upper boundary of the 95% confidence interval of the subhazard ratio). The key secondary outcome was clinically relevant bleeding, assessed in a superiority analysis.</p><p><strong>Results: </strong>A total of 1766 patients underwent randomization at a median time since the index event of 8.0 months (interquartile range, 6.5 to 12.6); 866 patients were assigned to the reduced-dose group, and 900 to the full-dose group. The median treatment duration was 11.8 months (interquartile range, 8.3 to 12.1). Recurrent venous thromboembolism occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 (cumulative incidence, 2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41; P = 0.001 for noninferiority). Clinically relevant bleeding occurred in 102 patients (cumulative incidence, 12.1%) in the reduced-dose group and in 136 (cumulative incidence, 15.6%) in the full-dose group (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P = 0.03). Mortality was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio, 0.96; 95% CI, 0.86 to 1.06).</p><p><strong>Conclusions: </strong>Extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent venous thromboembolism in patients with active cancer. The reduced dose led to a lower incidence of clinically relevant bleeding complications than the full dose. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; API-CAT ClinicalTrials.gov number, NCT03692065.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"New England Journal of Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1056/NEJMoa2416112","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: In patients with active cancer and venous thromboembolism, whether extended treatment with a reduced dose of an oral anticoagulant is effective in preventing recurrent thromboembolic events and decreasing bleeding is unclear.
Methods: We conducted a randomized, double-blind, noninferiority trial with blinded central outcome adjudication. Consecutive patients with active cancer and proximal deep-vein thrombosis or pulmonary embolism who had completed at least 6 months of anticoagulant therapy were randomly assigned in a 1:1 ratio to receive oral apixaban at a reduced (2.5 mg) or full (5.0 mg) dose twice daily for 12 months. The primary outcome was centrally adjudicated fatal or nonfatal recurrent venous thromboembolism, assessed in a noninferiority analysis (margin of 2.00 for the upper boundary of the 95% confidence interval of the subhazard ratio). The key secondary outcome was clinically relevant bleeding, assessed in a superiority analysis.
Results: A total of 1766 patients underwent randomization at a median time since the index event of 8.0 months (interquartile range, 6.5 to 12.6); 866 patients were assigned to the reduced-dose group, and 900 to the full-dose group. The median treatment duration was 11.8 months (interquartile range, 8.3 to 12.1). Recurrent venous thromboembolism occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 (cumulative incidence, 2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41; P = 0.001 for noninferiority). Clinically relevant bleeding occurred in 102 patients (cumulative incidence, 12.1%) in the reduced-dose group and in 136 (cumulative incidence, 15.6%) in the full-dose group (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P = 0.03). Mortality was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio, 0.96; 95% CI, 0.86 to 1.06).
Conclusions: Extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent venous thromboembolism in patients with active cancer. The reduced dose led to a lower incidence of clinically relevant bleeding complications than the full dose. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; API-CAT ClinicalTrials.gov number, NCT03692065.).
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