Low-molecular-weight-heparin versus a coumarin for the prevention of recurrent venous thromboembolism in high- and low-risk patients with active cancer: a post hoc analysis of the CLOT Study

Abstract

In patients with active cancer and acute venous thromboembolism (VTE), the low-molecular-weight-heparin (LMWH) dalteparin is more effective than vitamin K antagonist (VKA) in reducing the risk of recurrent venous thromboembolism (rVTE) without increasing the risk of bleeding. However, the relative benefit of LMWH versus VKA in patients with active cancer at high or low risk of rVTE and bleeding is unclear. This post hoc analysis used data from the CLOT study to explore the efficacy and safety of LMWH versus VKA in preventing recurrent thrombosis in high- and low-risk patients with active cancer. High-risk patients were defined by metastatic disease and/or antineoplastic treatment at baseline; low-risk patients presented with neither. Among high-risk patients, rVTE occurred in 25/318 (8%) (LMWH) versus 53/314 (17%) (VKA) (hazard ratio, 0.44; p = 0.001). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 40% (LMWH) versus 41% (VKA). In low-risk patients, 2/20 (10%) (LMWH) had rVTE versus 0/24 (0%) (VKA) (hazard ratio, not estimable; p = 0.998). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 20% (LMWH) versus 29% (VKA). In patients with cancer-associated thrombosis at high risk of rVTE and bleeding, the LMWH dalteparin was more effective than VKA in reducing the risk of rVTE without increasing the risk of bleeding. No difference in rate of rVTE or bleeding was observed between LMWH and VKA among low-risk patients.

Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms

“…Although the existing clinical trials are limited, their findings suggest a positive impact of anticoagulation in cancer patients. Nevertheless, this advantage is not the same in all cases, since some histological types of tumor appear to be extra responsive to the action of anticoagulation therapy than others in the early stages of neoplastic development [120][121][122].…”

“…This has led to increasing interest in the potential benefits of anticoagulation in this field. Concerning cancer patients, several researchers [120][121][122] have reported a substantial risk of recurrent thrombosis in such individuals despite oral anticoagulation therapy. On comparing low molecular weight heparin (LMWH) versus coumarin, dalteparin was seen to be more active than an oral anticoagulant in risk reduction of recurrent thromboembolism, apart from incrementing bleeding risk.…”

Concurrence of Gastric Cancer and Incidental Pulmonary Embolism May Be a Prognostic Factor for Advanced Gastric Cancer Patients with Incidental Pulmonary Embolism

“…Because of the similarities in overall mortality, major bleeding, and recurrent VTE in patients with IPE and those with symptomatic PE, the general consensus is to use the same treatment strategy for both sets of patients. 13,[32][33][34] Primarily, on the basis of the results of the CLOT (Randomized Comparison of LMWH versus Oral Anticoagulant Therapy for the Prevention of Recurrent VTE in Patients with Cancer) trial, [35][36][37] evidence-based guidelines recommend at least 6 months of LMWH treatment for patients with VTE and cancer, and that LMWH is preferable to warfarin-based treatment.…”

Prevention and treatment of thrombosis in cancer and oncohematological patients

“…Выделяют следующие факторы риска тромбозов: 1) связанные с развитием опухоли; 2) связанные с па циентом; 3) связанные с лечением [27][28][29].…”

“…При этом длительность лечения опухольассоциированного тромбоза должна составлять 3-6 мес, до тех пор, пока больной получает активное противоопухолевое лече ние или действуют дополнительные факторы риска развития тромбозов [16,18,31]. В исследовании CLOT показано, что вероятность клинически выраженного рецидива проксимального тромбоза глубоких вен или тромбоэмболии легочной артерии у онкологических больных, получавших НМГ (далтепарин натрия), до стоверно ниже (8 %) по сравнению с таковой при по следовательной терапии далтепарином натрия и анта гонистами витамина K -15,8 % [29,43].…”