Florian Posch1, Oliver Königsbrügge1, Christoph Zielinski2, Ingrid Pabinger1, Cihan Ay3. 1. Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. 2. Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. 3. Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. Electronic address: cihan.ay@meduniwien.ac.at.
Abstract
INTRODUCTION: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA) are current treatment options for cancer patients suffering from acute venous thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for the treatment of VTE in cancer patients, particular in comparison with the current standard of care which is LMWH, remains unclear. In this network meta-analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for the treatment of cancer-associated VTE. METHODS: A pre-specified search protocol identified 10 randomized controlled trials including 3242 cancer patients. Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were analyzed using a random-effects meta-regression model. RESULTS: LMWH emerged as significantly superior to VKA with respect to risk reduction of recurrent VTE (RR=0.60, 95%CI:0.45-0.79, p<0.001), and its safety was comparable to VKA (RR=1.08, 95%CI:0.70-1.66, p=0.74). For the DOAC vs. VKA efficacy and safety comparison, the relative risk estimates were in favor of DOAC, but had confidence intervals that still included equivalence (RR for recurrent VTE=0.65, 95%CI:0.38-1.09, p=0.10; RR for major bleeding=0.72, 95%CI:0.39-1.37, p=0.32). In the indirect network comparison between DOAC and LMWH, the results indicated comparable efficacy (RR=1.08, 95%CI:0.59-1.95, p=0.81), and a non-significant relative risk towards improved safety with DOAC (RR=0.67, 95%CI:0.31-1.46, p=0.31). The results prevailed after adjusting for different risk of recurrent VTE and major bleeding between LMWH vs. VKA and DOAC vs. VKA studies. CONCLUSION: The efficacy and safety of LMWH and DOACs for the treatment of VTE in cancer patients may be comparable. FUNDING: Austrian Science Fund (FWF-SFB-54).
INTRODUCTION: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA) are current treatment options for cancerpatients suffering from acute venous thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for the treatment of VTE in cancerpatients, particular in comparison with the current standard of care which is LMWH, remains unclear. In this network meta-analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for the treatment of cancer-associated VTE. METHODS: A pre-specified search protocol identified 10 randomized controlled trials including 3242 cancerpatients. Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were analyzed using a random-effects meta-regression model. RESULTS:LMWH emerged as significantly superior to VKA with respect to risk reduction of recurrent VTE (RR=0.60, 95%CI:0.45-0.79, p<0.001), and its safety was comparable to VKA (RR=1.08, 95%CI:0.70-1.66, p=0.74). For the DOAC vs. VKA efficacy and safety comparison, the relative risk estimates were in favor of DOAC, but had confidence intervals that still included equivalence (RR for recurrent VTE=0.65, 95%CI:0.38-1.09, p=0.10; RR for major bleeding=0.72, 95%CI:0.39-1.37, p=0.32). In the indirect network comparison between DOAC and LMWH, the results indicated comparable efficacy (RR=1.08, 95%CI:0.59-1.95, p=0.81), and a non-significant relative risk towards improved safety with DOAC (RR=0.67, 95%CI:0.31-1.46, p=0.31). The results prevailed after adjusting for different risk of recurrent VTE and major bleeding between LMWH vs. VKA and DOAC vs. VKA studies. CONCLUSION: The efficacy and safety of LMWH and DOACs for the treatment of VTE in cancerpatients may be comparable. FUNDING: Austrian Science Fund (FWF-SFB-54).
Authors: Harry R Büller; Hervé Décousus; Michael A Grosso; Michele Mercuri; Saskia Middeldorp; Martin H Prins; Gary E Raskob; Sebastian M Schellong; Lee Schwocho; Annelise Segers; Minggao Shi; Peter Verhamme; Phil Wells Journal: N Engl J Med Date: 2013-08-31 Impact factor: 91.245
Authors: Russell D Hull; Graham F Pineo; Rollin F Brant; Andrew F Mah; Natasha Burke; Richard Dear; Turnly Wong; Roy Cook; Susan Solymoss; Man-Chiu Poon; Gary Raskob Journal: Am J Med Date: 2007-01 Impact factor: 4.965
Authors: Marc Carrier; Chris Cameron; Aurélien Delluc; Lana Castellucci; Alok A Khorana; Agnes Y Y Lee Journal: Thromb Res Date: 2014-10-08 Impact factor: 3.944
Authors: Agnes Y Y Lee; Mark N Levine; Ross I Baker; Chris Bowden; Ajay K Kakkar; Martin Prins; Frederick R Rickles; Jim A Julian; Susan Haley; Michael J Kovacs; Michael Gent Journal: N Engl J Med Date: 2003-07-10 Impact factor: 91.245
Authors: D Farge; P Debourdeau; M Beckers; C Baglin; R M Bauersachs; B Brenner; D Brilhante; A Falanga; G T Gerotzafias; N Haim; A K Kakkar; A A Khorana; R Lecumberri; M Mandala; M Marty; M Monreal; S A Mousa; S Noble; I Pabinger; P Prandoni; M H Prins; M H Qari; M B Streiff; K Syrigos; H Bounameaux; H R Büller Journal: J Thromb Haemost Date: 2013-01 Impact factor: 5.824
Authors: Sam Schulman; Ajay K Kakkar; Samuel Z Goldhaber; Sebastian Schellong; Henry Eriksson; Patrick Mismetti; Anita Vedel Christiansen; Jeffrey Friedman; Florence Le Maulf; Nuala Peter; Clive Kearon Journal: Circulation Date: 2013-12-16 Impact factor: 29.690
Authors: Martin H Prins; Anthonie W A Lensing; Tim A Brighton; Roger M Lyons; Jeffrey Rehm; Mila Trajanovic; Bruce L Davidson; Jan Beyer-Westendorf; Ákos F Pap; Scott D Berkowitz; Alexander T Cohen; Michael J Kovacs; Philip S Wells; Paolo Prandoni Journal: Lancet Haematol Date: 2014-09-28 Impact factor: 18.959
Authors: A Romera; M A Cairols; R Vila-Coll; X Martí; E Colomé; A Bonell; O Lapiedra Journal: Eur J Vasc Endovasc Surg Date: 2009-01-01 Impact factor: 7.069
Authors: Hanno Riess; Cihan Ay; Rupert Bauersachs; Cecilia Becattini; Jan Beyer-Westendorf; Francis Cajfinger; Ian Chau; Alexander T Cohen; Alok A Khorana; Anthony Maraveyas; Marcos Renni; Annie M Young Journal: Oncologist Date: 2018-04-12
Authors: Mariasanta Napolitano; Giorgia Saccullo; Marco Marietta; Monica Carpenedo; Giancarlo Castaman; Elisabetta Cerchiara; Antonio Chistolini; Laura Contino; Valerio De Stefano; Anna Falanga; Augusto B Federici; Elena Rossi; Rita Santoro; Sergio Siragusa; Valerio De Stefano; Anna Falanga; Alberto Tosetto; Giuseppe Avvisati; Monica Carpenedo; Augusto B Federici; Marco Marietta; Mariasanta Napolitano; Elena Rossi; Cristina Santoro; Giancarlo Castaman; Elisabetta Cerchiara; Antonio Chistolini; Laura Contino; Maria Gabriella Mazzucconi; Ilaria Nichele; Laura Russo; Roberto Santi; Rita Carlotta Santoro; Sergio Siragusa; Giuseppe Tagariello Journal: Blood Transfus Date: 2018-10-24 Impact factor: 3.443
Authors: A Franco-Moreno; L Cabezón-Gutiérrez; M Palka-Kotlowsa; M Villamayor-Delgado; M García-Navarro Journal: J Thromb Thrombolysis Date: 2019-04 Impact factor: 2.300