Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism
Por:
Mahé, I, Carrier, M, Mayeur, D, Chidiac, J, Vicaut, E, Falvo, N, Sanchez, O, Grange, C, Monreal, M, López-Núñez, JJ, Otero-Candelera, R, Le Gal, G, Yeo, ER, Righini, M, Robert-Ebadi, H, Huisman, MV, Klok, FA, Westerweel, P, Agnelli, G, Becattini, C, Bamias, A, Syrigos, K, Szmit, S, Torbicki, A, Verhamme, P, Maraveyas, A, Cohen, AT, Ay, C, Chapelle, C, Meyer, G, Couturaud, F, Mismetti, P, Girard, P, Bertoletti, L and Laporte, S
Publicada:
10 abr 2025
Ahead of Print:
1 mar 2025
Resumen:
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.)
Filiaciones:
Mahé, I:
Hop Louis Mourier, Assistance Publ Hop Paris AP HP, Serv Med Interne, Colombes, France
Univ Paris Cite, Paris, ON, Canada
Paris Cardiovasc Res Ctr, INSERM Unite Mixte Rech S970, Team Endotheliopathy & Hemostasis Disorders, Paris, France
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Carrier, M:
Univ Ottawa, Ottawa Hosp Res Inst, Dept Med, Ottawa, ON, Canada
Mayeur, D:
Ctr Georges Francois Leclerc, Dijon, France
Unicanc AFSOS Support Care Res Grp, Begles, France
Chidiac, J:
Hop Louis Mourier, Assistance Publ Hop Paris AP HP, Serv Med Interne, Colombes, France
Vicaut, E:
Univ Paris Cite, Paris, ON, Canada
Unite Rech Clin Lariboisiere St Louis, AP HP, Paris, France
Falvo, N:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Ctr Hosp Univ CHU Dijon Bourgogne, Dept Vasc Pathol, Dijon, France
Sanchez, O:
Univ Paris Cite, Paris, ON, Canada
Paris Cardiovasc Res Ctr, INSERM Unite Mixte Rech S970, Team Endotheliopathy & Hemostasis Disorders, Paris, France
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Hop Europeen Georges Pompidou, AP HP, Serv Pneumol & Soins Intensifs, Paris, France
Grange, C:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Hosp Civils Lyon, Serv Med Interne & Med Vasc, Lyon, France
Monreal, M:
Hosp Univ Germans Trias i Pujol, Inst Recerca Germans Trias i Pujol, Dept Internal Med, Badalona, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Univ Catolica San Antonio Murcia, Murcia, Spain
:
Hosp Univ Germans Trias i Pujol, Inst Recerca Germans Trias i Pujol, Dept Internal Med, Badalona, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Resp, Madrid, Spain
Otero-Candelera, R:
Ctr Invest Biomed Red Enfermedades Resp, Madrid, Spain
Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed, Seville, Spain
Le Gal, G:
Univ Ottawa, Ottawa Hosp Res Inst, Dept Med, Ottawa, ON, Canada
Yeo, ER:
Univ Hlth Network, Toronto Gen Hosp, Toronto, ON, Canada
Righini, M:
Geneva Univ Hosp, Fac Med, Div Angiol & Hemostasis, Geneva, Switzerland
Robert-Ebadi, H:
Geneva Univ Hosp, Fac Med, Div Angiol & Hemostasis, Geneva, Switzerland
Huisman, MV:
Leiden Univ, Dept Med, Div Thrombosis & Hemostasis, Med Ctr, Leiden, Netherlands
Klok, FA:
Leiden Univ, Dept Med, Div Thrombosis & Hemostasis, Med Ctr, Leiden, Netherlands
Westerweel, P:
Albert Schweitzer Hosp Dordrecht, Dept Internal Med, Dordrecht, Netherlands
Agnelli, G:
Univ Perugia, Internal Vasc & Emergency Med Stroke Unit, Perugia, Italy
Becattini, C:
Univ Perugia, Internal Vasc & Emergency Med Stroke Unit, Perugia, Italy
Bamias, A:
Natl & Kapodistrian Univ Athens, ATTIKON Univ Hosp, Propaedeut Dept Med 2, Athens, Greece
Syrigos, K:
Natl & Kapodistrian Univ, Sotiria Gen Hosp Chest Dis, Dept Internal Med, Athens, Greece
Szmit, S:
European Hlth Ctr, Ctr Postgrad Med Educ, Dept Pulm Circulat Thromboembol Dis & Cardiol, Otwock, Poland
Ctr Postgrad Med Educ, Dept Cardiooncol, Warsaw, Poland
Torbicki, A:
European Hlth Ctr, Ctr Postgrad Med Educ, Dept Pulm Circulat Thromboembol Dis & Cardiol, Otwock, Poland
Verhamme, P:
Univ Hosp Leuven, Vasc Med & Hemostasis, Leuven, Belgium
Maraveyas, A:
Hull Univ Teaching Hosp NHS Trust, Hull York Med Sch, Kingston Upon Hull, England
Cohen, AT:
Kings Coll London, Guys & St Thomas NHS Fdn Trust Hosp, London, England
Ay, C:
Med Univ Vienna, Comprehens Canc Ctr Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria
Chapelle, C:
CHU St Etienne, Serv Pharmacol Clin, St Etienne, France
Univ Jean Monnet, INSERM Unite 1059, Mines St Etienne, Sante Ingn Biol St Etienne SAINBIOSE, St Etienne, France
Meyer, G:
Univ Paris Cite, Paris, ON, Canada
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Couturaud, F:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Univ Brest, INSERM Unite 1412, Ctr Invest Clin CIC, INSERM Unite 1304,Grp Etud Thrombose Bretagne Occi, Brest, France
CHU Brest, Dept Med Interne & Pneumol, Brest, France
Mismetti, P:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Univ Jean Monnet, INSERM Unite 1059, Mines St Etienne, Sante Ingn Biol St Etienne SAINBIOSE, St Etienne, France
CHU St Etienne, Serv Med Vasc & Therapeut, St Etienne, France
CHU St Etienne, INSERM CIC 1408, St Priest En Jarez, France
Girard, P:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Inst Mutualiste Montsouris, Dept Thorac, Paris, France
Bertoletti, L:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
Univ Jean Monnet, INSERM Unite 1059, Mines St Etienne, Sante Ingn Biol St Etienne SAINBIOSE, St Etienne, France
CHU St Etienne, Serv Med Vasc & Therapeut, St Etienne, France
CHU St Etienne, INSERM CIC 1408, St Priest En Jarez, France
Laporte, S:
French Clin Res Infrastructure Network, Invest Network Venous Thromboembolism, St Etienne, France
CHU St Etienne, Serv Pharmacol Clin, St Etienne, France
Univ Jean Monnet, INSERM Unite 1059, Mines St Etienne, Sante Ingn Biol St Etienne SAINBIOSE, St Etienne, France
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