Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer
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- Deborah Schrag
- Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston, Massachusetts
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- Hajime Uno
- Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston, Massachusetts
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- Rachel Rosovsky
- Massachusetts General Hospital and Harvard Medical School, Boston
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- Cynthia Rutherford
- University of Texas Southwestern, Dallas
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- Kristen Sanfilippo
- Washington University School of Medicine, St Louis, Missouri
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- John L. Villano
- University of Kentucky School of Medicine, Lexington
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- Monic Drescher
- Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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- Nagesh Jayaram
- Southeastern Medical Oncology Center, Winston-Salem, North Carolina
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- Chris Holmes
- University of Vermont Medical Center, Billings
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- Lawrence Feldman
- University of Illinois School of Medicine, Chicago
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- Ottavia Zattra
- Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston, Massachusetts
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- Haley Farrar-Muir
- Massachusetts General Hospital and Harvard Medical School, Boston
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- Christine Cronin
- Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston, Massachusetts
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- Ethan Basch
- UNC Lineberger Cancer Center Comprehensive Cancer Center, Chapel Hill, North Carolina
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- Anna Weiss
- Brigham and Women’s Hospital, Boston, Massachusetts
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- Jean M. Connors
- Brigham and Women’s Hospital, Boston, Massachusetts
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- Kenneth N. M. Sumida
- for the CANVAS Investigators
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- Robert C. Martin
- for the CANVAS Investigators
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- Maria T. Grosse Perdekamp
- for the CANVAS Investigators
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- Ben Yan
- for the CANVAS Investigators
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- Donald Doll
- for the CANVAS Investigators
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- Anna Ninny J. Abraham
- for the CANVAS Investigators
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- Tzu-Fei Wang
- for the CANVAS Investigators
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- Ryan M. Jones
- for the CANVAS Investigators
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- Abirami Sivapiragasm
- for the CANVAS Investigators
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- Ellis G. Levine
- for the CANVAS Investigators
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- Kamal Haider
- for the CANVAS Investigators
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- Paula M. Rosenblatt
- for the CANVAS Investigators
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- James W. Fleshman
- for the CANVAS Investigators
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- William J. Irvin
- for the CANVAS Investigators
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- Meghana Raghavendra
- for the CANVAS Investigators
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- Andrea R. Dean
- for the CANVAS Investigators
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- Michael M. Goodman
- for the CANVAS Investigators
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- Susanna Hong
- for the CANVAS Investigators
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- Lisa M. Baumann Kreuziger
- for the CANVAS Investigators
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- Isaac A. Bowman
- for the CANVAS Investigators
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- Steve K. M. S. Lo
- for the CANVAS Investigators
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- Alfonso J. Tafur
- for the CANVAS Investigators
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- Anthony J. Jaslowski
- for the CANVAS Investigators
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- Misbah U. Qadir
- for the CANVAS Investigators
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- Anasuya Gunturi
- for the CANVAS Investigators
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- Moniba Nazeef
- for the CANVAS Investigators
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- Kelvin Raybon
- for the CANVAS Investigators
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- Robert I. Kaplan
- for the CANVAS Investigators
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- Astrid C. Andreescu
- for the CANVAS Investigators
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- Dan Sotirescu
- for the CANVAS Investigators
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- John C. Keech
- for the CANVAS Investigators
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- Albert S. Malcolm
- for the CANVAS Investigators
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- Florin D. Andreca
- for the CANVAS Investigators
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- Vinay I. Shah
- for the CANVAS Investigators
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- Andrew D. Leavitt
- for the CANVAS Investigators
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- Benjamin T. Marchello
- for the CANVAS Investigators
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- Daniel Flora
- for the CANVAS Investigators
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- Douglas Weckstein
- for the CANVAS Investigators
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- Neelesh S. Bangalore
- for the CANVAS Investigators
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- Jessica Belmonte
- for the CANVAS Investigators
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- Aldemar Montero
- for the CANVAS Investigators
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- Surbhi P. Shah
- for the CANVAS Investigators
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- Michael Constantine
- for the CANVAS Investigators
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- Meredith Faggen
- for the CANVAS Investigators
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- Frederick Briccetti
- for the CANVAS Investigators
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- Christopher Lathan
- for the CANVAS Investigators
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- Robert L. D'Agostino
- for the CANVAS Investigators
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- Randolph Fenninger
- for the CANVAS Investigators
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- Thomas Delate
- for the CANVAS Investigators
書誌 事項
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タイトル
別名 -
- A Randomized Clinical Trial
説明
<jats:sec><jats:title>Importance</jats:title><jats:p>In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, −2.7%; 1-sided 95% CI, −100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, −0.4%; 1-sided 95% CI, –100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02744092">NCT02744092</jats:ext-link></jats:p></jats:sec>
収録 刊行 物
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- JAMA
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JAMA 329 (22), 1924-, 2023-06-13
American Medical Association (AMA)