Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer

• Published in: Cochrane database of systematic reviews 2018-06, Vol.6 (6), p.CD006650
• Main Authors: Kahale, Lara A, Hakoum, Maram B, Tsolakian, Ibrahim G, Matar, Charbel F, Terrenato, Irene, Sperati, Francesca, Barba, Maddalena, Yosuico, Victor Ed, Schünemann, Holger, Akl, Elie A
• Format: Article
• Language: English
• Subjects: 'ORPHAN' TOPICS CURRENTLY BEING ADDRESSED; Administration, Oral; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Azetidines - therapeutic use; Benzimidazoles - therapeutic use; Benzylamines - therapeutic use; beta-Alanine - analogs & derivatives; beta-Alanine - therapeutic use; Cancer; Child health; Dabigatran - therapeutic use; Heart & circulation; Hemorrhage - chemically induced; Heparin, Low-Molecular-Weight - therapeutic use; Humans; Neoplasms - complications; Oligosaccharides - therapeutic use; Randomized Controlled Trials as Topic; Venous Thromboembolism - drug therapy; Venous Thromboembolism - etiology; Venous Thromboembolism - mortality; Vitamin K - antagonists & inhibitors
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD006650.pub5

Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments. To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer. We conducted a literature search including a major electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE (Ovid), and Embase (Ovid); handsearching conference proceedings; checking references of included studies; use of the 'related citation' feature in PubMed and a search for ongoing studies in trial registries. As part of the living systematic review approach, we run searches continually, incorporating new evidence after it is identified. Last search date 14 May 2018. Randomized controlled trials (RCTs) assessing the benefits and harms of long-term treatment with LMWHs, DOACs or VKAs in people with cancer and symptomatic VTE. We extracted data in duplicate on study characteristics and risk of bias. Outcomes included: all-cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and health-related quality of life (QoL). We assessed the certainty of the evidence at the outcome level following the GRADE approach (GRADE handbook). Of 15,785 citations, including 7602 unique citations, 16 RCTs fulfilled the eligibility criteria. These trials enrolled 5167 people with cancer and VTE.Low molecular weight heparins versus vitamin K antagonistsEight studies enrolling 2327 participants compared LMWHs with VKAs. Meta-analysis of five studies probably did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on mortality up to 12 months of follow-up (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.13; risk difference (RD) 0 fewer per 1000, 95% CI 45 fewer to 48 more; moderate-certainty evidence). Meta-analysis of four studies did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on major bleeding (RR 1.09, 95% CI 0.55 to 2.12; RD 4 more per 1000, 95% CI 19 fewer to 48 more, moderate-certainty evidence) or minor bleeding (RR 0.78, 95% CI 0.47 to 1.27; RD 38 fewer per 1000, 95% CI 92 fewer to 47 more; low-certainty evidence), or thrombocytopenia (RR 0.94, 95% CI 0.52 to 1.69). Meta-analysis of five studies showed that LMWHs probably reduced the recurrence of VTE compared to VKAs (RR 0.58, 95% CI 0.43 to 0.77; RD 53 f