International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

Abstract

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at an increased risk of developing VTE and are more likely to have a recurrence of VTE and bleeding while taking anticoagulants. Management of VTE in patients with cancer is a major therapeutic challenge and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME), established to reduce the global burden of VTE in patients with cancer, published international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis. The rapid global adoption of direct oral anticoagulants for management of VTE in patients with cancer is an emerging treatment trend that needs to be addressed based on the current level of evidence. In this Review, we provide an update of the ITAC-CME consensus recommendations based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. These guidelines aim to address in-hospital and outpatient cancer-associated VTE in specifi c subgroups of patients with cancer.

Management of cancer-associated venous thromboembolism – a case-based practical approach

“…Several subsequent studies therefore investigated whether long-term anticoagulation with LMWH is more safe and effi cacious than standard treatment, i. e. initial parenteral anticoagulation with LMWH at therapeutic dosages followed by overlapping oral anticoagulation with VKA titrated to maintain the international normalized ratio (INR) between two and three. The CANTHANOX study, which started patient recruitment more than 20 years ago and compared three months of enoxaparin 1.5 mg/kg body weight once daily with warfarin [14], was followed by two smaller studies, ON-CENOX (enoxaparin) and LITE (tinzaparin) [15,16], and the two pivotal LMWH trials, CLOT (dalteparin) and CATCH (tinzaparin) [12,13], all of which resulted in specifi c guideline recommendations for the treatment of cancer-associated VTE [7][8][9][10][11].…”

“…As a result from the CLOT and CATCH and the other smaller trials, long-term treatment with LMWH is considered safer and more effi cacious than standard VKA therapy in patients with cancer-associated VTE [7][8][9][10][11]. Although dalteparin and tinzaparin are the only two LMWHs formally approved for the long-term treatment and secondary prevention of cancer-associated VTE, most guideline recommendations refer to LMWH as a class of anticoagulants rather than pointing out specifi c agents.…”

“…To date, no study has specifi cally evaluated the optimal duration of anticoagulation in the setting of cancer-associated VTE. Based on the inconsistent data, guidelines diff er with regard to treatment duration, with some recommending not less than three months [8] and others recommending a minimum of six months [7,9,10], at least in cases of PE [11].…”

“…At present, long-term anticoagulation with low-molecular-weight heparin (LMWH) represents the standard of care in the treatment of cancer-associated VTE [7][8][9][10][11], because several prospective, randomized trials have demonstrated an improved safety and effi cacy profi le of LMWH compared to VKA in this vulnerable patient population [12][13][14][15][16]. However, based on the desire to off er cancer patients a more comfortable route of drug administration, the use of direct oral anticoagulants (DOACs) has emerged as an attractive alternative to parenteral anticoagulation with LMWH in clinical practice, even more so as healthcare resources related to the costs of prescribed daily dosages are signifi cantly lower with this class of anticoagulants.…”

Simultaneous large bi-atrial device-related thrombi

“…Still, actual recommendations on DOACs advise caution when used in cancer patients [4]. As evidence for the treatment of device-related thrombosis other than central venous catheter-associated thrombosis in patients with cancer is limited, the presented patient was referred to the regional hospital for the initiation of an anticoagulation using (low-molecular weight) heparins, in accordance to current recommendations on the treatment of cancer-associated VTE [5][6].…”