HHE Cardiovascular supplement 2018 - Page 19

cardiovascular Preventing and treating VTE in patients with renal insufficiency Patients with chronic kidney disease have an elevated risk for bleeding with declining glomerular filtration rate, even in the absence of anticoagulants, but also have an elevated risk of thromboembolism Piet Habbel Cecilia Bozzetti Hanno Riess Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine Berlin, Germany Chronic kidney disease (CKD), a reduction in renal function with decreasing glomerular filtration rate (GFR) is increasing in incidence as well as in prevalence due to a growing elderly population. The progressive reduction in GFR to less than 60ml/min (modest renal insufficiency; mRI) or severe renal insufficiency (sRI; with GFR <30ml/min) may lead to end stage renal disease (ESRD) with a requirement for chronic haemodialysis (CHD). In parallel with progressing age, there is an increase in CKD, elective and non-elective surgeries, non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE). Of note, CKD and AF as well as CKD and VTE are not independent conditions, but, in both situations, positive bidirectional relationships have been proved. 1,2 Patients undergoing major surgery have an elevated risk for thromboembolic events. In these patients and those suffering any VTE, anticoagulant therapy is highly effective in the primary and secondary prevention of thromboembolism. Yet, this efficacy of anticoagulant drugs also exposes patients to an increased risk of anticoagulant-associated bleeding. 3 This short review will neither address the appropriate anticoagulation in the context of CHD nor the problem of how to adapt anticoagulation in acute kidney failure, but will discuss specific aspects of anticoagulant treatment in patients with CKD at risk for acute or recurrent VTE. 19 HHE 2018 | hospitalhealthcare.com Anticoagulant drugs and renal insufficiency For a long time parenteral drugs such as unfractionated heparin (UFH), low-molecular- weight heparins (LMWH), or fondaparinux (FPX) were used for acute initiation of anticoagulation therapy, which was then switched to an oral vitamin K antagonist (VKA) such as warfarin. Nowadays direct oral anticoagulants (DOACs) have become available for primary and secondary prevention as recently reviewed by Moss and colleagues. 4 These anticoagulant drugs do not only differ in their mode of action and the time course of anticoagulant activity but also in the degree of drug–drug interactions as well as in the dependency of their pharmacokinetic parameters on kidney function (Table 1). Most anticoagulant drugs (LMWH, FPX, DOACs) can accumulate in patients with impaired renal capacity. 5 The recent randomised Phase III landmark studies in VTE 6 and the supporting evidence in AF, 7 demonstrated the efficacy and safety of anticoagulant drugs but excluded patients with sRI or even ESRD. With the exception of LMWH – where some data are available 8,9 – recommendations on how to treat patients with markedly reduced GFR having an urgent need for anticoagulation are based mainly on considerations of pharmacokinetic data, extrapolation of clinical study results in subgroup analyses of patients with mRI, and case series. Patients with CKD have an elevated risk for bleeding with declining GFR, even FR'6V6PbFF&&F2G'Vw2'WB66VVFfPVWfFVB&6bF&&V&Ɨ6"FW&Vf&RF&VvWfVFbFRFVN( 2FfGV&6&fR66W&rF&&V&Ɩ2WfVG0B&VVFr6Ɩ6F22F&P&V6VFVB&"FFR66RbG'Vr@F6Rf"F6wVF&VfW"F2&6&fR6VB&R&R76W76VB&VwV"&62GVRFFffW&VB&6G֖2&W'FW0bF6wVBG'Vw2F&RFR&6`67VVF&W7VFr7&V6VB&VVFp&6FffW'2rFRf&RG'Vw2BVVG0F&R66FW&VBFVG2vFW7FFV@te"bS֖F&R"FR֗66VVW2tfRFffW&V@V7V"vVvBF7G&'WF2ffV7FrFV W7&WF'FRFW2B&W7VFrখfW'6R&VF6&WGvVVV7V"vVv@B&V6V&6R&VfW"e2vW bƖfRBvW"&6b67VVF