Key Words: Direct oral anticoagulants, Thromboembolic disease, Low molecular weight heparin, cancer, Epistemonikos, GRADE
Abstract
Introduction
Low molecular weight heparin is currently the standard therapy for the primary prevention of thromboembolic disease in cancer patients. The use of direct-acting anticoagulants could be an alternative, but its efficacy and safety profile in these types of patients remains unclear.
Methods
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from identified reviews, analyzed data from primary studies, performed a meta-analysis, and prepared a summary table of results using the GRADE method.
Results and conclusions
We identified four systematic reviews that together included two primary studies, of which both correspond to trials. We conclude that the use of direct-acting oral anticoagulants probably increases the outcome of major bleeding and likely slightly increases the risk of thromboembolic disease. No studies were found that evaluated the outcome of quality of life or mortality.
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Introducción
El uso de heparina de bajo peso molecular es actualmente la terapia estándar para prevención primaria de enfermedad tromboembólica en pacientes con cáncer. El uso de los anticoagulantes de acción directa podría ser una alternativa pero su perfil de eficacia y seguridad en este tipo de pacientes sigue siendo aún poco claro.
Métodos
Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.
Resultados y conclusiones
Identificamos cuatro revisiones sistemáticas que, en conjunto, incluyeron dos estudios primarios, los que corresponden a ensayos. Concluimos que el uso de anticoagulantes orales de acción directa probablemente aumenta el desenlace hemorragia mayor y probablemente aumenta levemente el riesgo de enfermedad tromboembólica. No se encontraron estudios que evaluaran el desenlace calidad de vida ni de mortalidad.
Authors:
Natalia Méndez[1], Constanza Norambuena[1], Symón Silva[1], Valentín López[1,2]
Affiliation:
[1] Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile
[2] Servicio de Medicina Interna, Hospital de Urgencia Asistencia Pública, Santiago, Chile
E-mail: nmendezr@uft.edu
Author address:
[1] Avenida Pedro de Valdivia 1509
Santiago, Chile
Citation: Méndez N, Norambuena C, Silva S, López V. Direct acting oral anticoagulants versus low molecular weight heparin for primary thromboprophylaxis in cancer patients. Medwave 2021;21(04):e8178 doi: 10.5867/medwave.2021.04.8178
Submission date: 27/10/2020
Acceptance date: 1/4/2021
Publication date: 3/5/2021
Origin: Not commissioned.
Type of review: Externally peer-reviewed by two reviewers, double-blind.
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- Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res. 2010 Jun;125(6):490-3. | CrossRef | PubMed |
- Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002 Nov- Dec;4(6):465-73. | CrossRef | PubMed |
- Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007 Mar;5(3):632-4. | CrossRef | PubMed |
- Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520. | CrossRef | PubMed |
- Yan YD, Zhang C, Shen L, Su YJ, Liu XY, Wang LW, et al. Net Clinical Benefit of Non-vitamin K Antagonist Oral Anticoagulants for Venous Thromboembolism Prophylaxis in Patients With Cancer: A Systematic Review and Trade-Off Analysis From 9 Randomized Controlled Trials. Front Pharmacol. 2018 Jun 12;9:575. | CrossRef | PubMed |
- Zeng J, Zhang X, Lip GYH, Shu X, Thabane L, Tian J, et al. Efficacy and Safety of Direct Oral Anticoagulants for Risk of Cancer-Associated Venous Thromboembolism. Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619853629. | CrossRef | PubMed |
- Sardar P, Chatterjee S, Herzog E, Pekler G, Mushiyev S, Pastori LJ, et al. New oral anticoagulants in patients with cancer: current state of evidence. Am J Ther. 2015 Nov-Dec;22(6):460-8. | CrossRef | PubMed |
- Franchini M, Bonfanti C, Lippi G. Cancer-associated thrombosis: investigating the role of new oral anticoagulants. Thromb Res. 2015 May;135(5):777-81. | CrossRef | PubMed |
- Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. | CrossRef | PubMed |
- Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. | CrossRef | PubMed |
- Li A, Manohar PM, Garcia DA, Lyman GH, Steuten LM. Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States. Thromb Res. 2019 Aug;180:37-42. | CrossRef | PubMed |
- Mandalà M, Falanga A, Roila F; ESMO Guidelines Working Group. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92. | CrossRef | PubMed |
- Guntupalli SR, Brennecke A, Behbakht K, Tayebnejad A, Breed CA, Babayan LM, et al. Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e207410. | CrossRef | PubMed |
Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res. 2010
Jun;125(6):490-3. | CrossRef | PubMed |Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of
malignancy: pathogenesis and current debate. Neoplasia. 2002 Nov-
Dec;4(6):465-73. | CrossRef | PubMed |Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is
a leading cause of death in cancer patients receiving outpatient chemotherapy. J
Thromb Haemost. 2007 Mar;5(3):632-4. | CrossRef | PubMed |Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous Thromboembolism Prophylaxis and
Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J
Clin Oncol. 2020 Feb 10;38(5):496-520. | CrossRef | PubMed |Yan YD, Zhang C, Shen L, Su YJ, Liu XY, Wang LW, et al. Net Clinical Benefit
of Non-vitamin K Antagonist Oral Anticoagulants for Venous Thromboembolism
Prophylaxis in Patients With Cancer: A Systematic Review and Trade-Off Analysis
From 9 Randomized Controlled Trials. Front Pharmacol. 2018 Jun 12;9:575. | CrossRef | PubMed |Zeng J, Zhang X, Lip GYH, Shu X, Thabane L, Tian J, et al. Efficacy and Safety
of Direct Oral Anticoagulants for Risk of Cancer-Associated Venous
Thromboembolism. Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619853629. | CrossRef | PubMed |Sardar P, Chatterjee S, Herzog E, Pekler G, Mushiyev S, Pastori LJ, et al. New oral anticoagulants in patients with cancer: current state of
evidence. Am J Ther. 2015 Nov-Dec;22(6):460-8. | CrossRef | PubMed |Franchini M, Bonfanti C, Lippi G. Cancer-associated thrombosis: investigating
the role of new oral anticoagulants. Thromb Res. 2015 May;135(5):777-81. | CrossRef | PubMed |Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, et al. Rivaroxaban for
thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb
7;368(6):513-23. | CrossRef | PubMed |Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, et al. Apixaban versus enoxaparin for thromboprophylaxis
in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. | CrossRef | PubMed |Li A, Manohar PM, Garcia DA, Lyman GH, Steuten LM. Cost effectiveness
analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment
of cancer associated thrombosis (CAT) in the United States. Thromb Res. 2019
Aug;180:37-42. | CrossRef | PubMed |Mandalà M, Falanga A, Roila F; ESMO Guidelines Working Group. Management of
venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice
Guidelines. Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92. | CrossRef | PubMed |Guntupalli SR, Brennecke A, Behbakht K, Tayebnejad A, Breed CA, Babayan LM, et al. Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative
Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant
Neoplasm: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e207410. | CrossRef | PubMed |
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