Abstract
Mechanical heart valves (MHV) require life-long anticoagulation with vitamin K antagonists (VKA), but anticoagulation management is complex in patients with cancer due to a high risk of thrombosis and bleeding. This is a retrospective, single-center study to assess anticoagulation management and thrombotic (stroke/valve thrombosis) and bleeding events in patients with active cancer and MHV. The incidence of thrombotic complications was compared to a control group (matched 1:1) of patients with MHV but without cancer. We included 48 patients, 60% of whom had aortic prostheses, 23% mitral prostheses and 17% both types. All patients received VKA as anticoagulant. With a median follow-up of 5.12 years, we observed two arterial thrombotic events (two strokes and no heart valve thrombosis). The 5-year incidence (95% confidence interval [CI]) of stroke/valve thrombosis was 5.7% (0.9–17.9%). The control group had a similar incidence of stroke/valve thrombosis (5-year incidence 7.9% [95%CI 2–19.8], p = 0.16). There were also 15 major bleeding episodes in the cancer group, 11 of which were related to a surgical procedure. The 5-year incidence (95% CI) of major bleeding was 32.9% (18.5–48%), and that of major bleeding unrelated to any procedure was 10.3% (3–23%). We found a low incidence of thrombotic events in this series of patients with active cancer and MHV who were anticoagulated with VKA. However, the incidence of bleeding was high, particularly in relation to invasive procedures.
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Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111:4902–4907. https://doi.org/10.1182/blood-2007-10-116327
Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, Panageas KS, DeAngelis LM (2017) Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol 70:926–938. https://doi.org/10.1016/j.jacc.2017.06.047
Donnellan E, Khorana AA (2017) Cancer and venous thromboembolic disease: a review. Oncologist. 22:199–207. https://doi.org/10.1634/theoncologist.2016-0214
Kamphuisen PW, Beyer-Westendorf J (2014) Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res 2(133 Suppl):49–55. https://doi.org/10.1016/S0049-3848(14)50009-6
Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients, J Thromb Haemost 3:692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x
Kim HT (2007) Cumulative incidence in competing risks data and competing risks regression analysis. Clin Cancer Res 13:559–565. https://doi.org/10.1158/1078-0432.CCR-06-1210
Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244
Ambrus DB, Reisman JI, Rose AJ (2016) The impact of new-onset cancer among veterans who are receiving warfarin for atrial fibrillation and venous thromboembolism. Thromb Res 144:21–26. https://doi.org/10.1016/j.thromres.2016.05.028
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM, Thomas JD (2017) American College of Cardiology/American Heart Association Task Force on Practice Guidelines, 2017 update of 2014 AHA/ACC guideline for the management of patients with valvular heart disease. J Am Coll Cardiol 63:e57–e185. https://doi.org/10.1016/j.jacc.2014.02.536
Cannegieter SC, Rosendaal FR, Briët E (1994) Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 89:635–641. https://doi.org/10.1161/01.CIR.89.2.635
Massel DR, Little SH (2013 (2013) Antiplatelet and anticoagulation for patients with prosthetic heart valves. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003464.pub2
Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A, Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized food and drug administration investigational device exemption trial. J Thorac Cardiovasc Surg 147 (2014). https://doi.org/10.1016/j.jtcvs.2014.01.004
Patell R, Gutierrez A, Rybicki L, Khorana AA (2017) Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol 120:2182–2186. https://doi.org/10.1016/j.amjcard.2017.08.038
Shah S, Norby FL, Datta YH, Lutsey PL, MacLehose RF, Chen LY, Alonso A (2018) Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv 2:200–209. https://doi.org/10.1182/bloodadvances.2017010694
Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AGG, Hasselblad V, Ortel TL (2015) BRIDGE investigators, perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 373:823–833. https://doi.org/10.1056/NEJMoa1501035
Rechenmacher SJ, Fang JC (2015) Bridging anticoagulation: primum non nocere. J Am Coll Cardiol 66:1392–1403. https://doi.org/10.1016/j.jacc.2015.08.002
Siegal D, Yudin J, Kaatz S, Douketis JD, Lim W, Spyropoulos AC (2012) Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation 126:1630–1639. https://doi.org/10.1161/CIRCULATIONAHA.112.105221
Hammerstingl C, Tripp C, Schmidt H, von der Recke G, Omran H (2007) Periprocedural bridging therapy with low-molecular-weight heparin in chronically anticoagulated patients with prosthetic mechanical heart valves: experience in 116 patients from the prospective BRAVE registry. J Heart Valve Dis 16:285–292
Hart EA, Jansen R, Meijs TA, Bouma BJ, Riezebos RK, Tanis W, van Boven WJP, Hindori V, Wiersma N, Dessing T, Westerink J, Chamuleau SAJ (2017) Anticoagulant bridging in left-sided mechanical heart valve patients. Int J Cardiol 232:121–126. https://doi.org/10.1016/j.ijcard.2017.01.042
Schulman JM, Majeed A, Mattsson E, Schulman S, Holmström M, Ågren A (2015) Strategies and outcomes of periprocedural bridging therapy with low-molecular-weight heparin in patients with mechanical heart valves. J Thromb Thrombolysis 40:430–436. https://doi.org/10.1007/s11239-015-1216-4
Lee Y-J, Park J, Uhm J-S, Kim J-Y, Pak H-N, Lee M-H, Sung J-H, Joung B (2016) Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy. Int J Cardiol 203:372–378. https://doi.org/10.1016/j.ijcard.2015.10.166
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Plaja, A., Berastegui, E., Nieto-Moragas, J. et al. Thromboembolism and bleeding in patients with cancer and mechanical heart valves. J Thromb Thrombolysis 47, 454–461 (2019). https://doi.org/10.1007/s11239-018-1790-3
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DOI: https://doi.org/10.1007/s11239-018-1790-3