HHE Cardiovascular supplement 2018 - Page 23

population seems to be questionable. The lack of obvious benefits supports the need for randomised trials in this setting as well as in patients with sRI, ESRD/CHD and acute VTE. In this context, it should be noted that embolism in AF is a permanent risk, whereas the risk of recurrent VTE decreases with time from the initial event. Thus, a transfer of study results in patients with AF to those with VTE needs critical reflection. A retrospective analysis following 1509 patients with VTE and sRI for three years demonstrated higher risks for relapse, major bleedings and mortality. 18 The available data comparing the initial anticoagulation in sRI or ESRD patients with acute VTE did not demonstrate any benefit for UFH compared with LMWH with regard to efficacy or safety but hint at an increased mortality in patients with sRI treated with UFH compared with LMWH. 19 Nevertheless, prospective randomised clinical trials are still unavailable. Until direct evidence is available, highly individual clinical decision- making must be recommended, especially with regard to the duration of full-dose anticoagulation therapy, because treatment efficacy in most patients suffering from acute VTE can be monitored by clinical, technical (ultrasound) and laboratory (D-dimer) investigations. Thus, a tailored duration and intensity of anticoagulation can be determined, thereby limiting the risk of haemorrhage due to prolonged anticoagulation. The availability of DOACs provides an alternative oral anticoagulation solution. 6 Again, subjects with sRI were excluded in the pitoval trials in VTE (and AF) with the thrombin inhibitor dabigatran (GFR <30ml/min) and the factor Xa inhibitors apixaban (GFR <25ml/min), edoxaban (GFR <30ml/min) or rivaroxaban (GFR <30ml/ min). 4-6 Based on published investigations of pharmacokinetics in patients with CHD, dose recommendations have been issued for ESRD. 20 For apixaban, the regular 5mg twice daily dose (2.5mg twice daily in patients > 80 years or < 60kg body weight) is suggested. Concerning rivaroxaban, a daily dose of 10mg in CHD patients resulted in drug exposure parameters similar to the findings for 20mg once a day in healthy volunteers. For edoxaban, a 15mg dose once daily in ESKD patients was found to be equivalent to References 1 Bansal N et al. Incident atrial fibrillation and risk of end- stage renal disease in adults with chronic kidney disease. Circulation 2013;127(5): 569–74. 2 Ocak G et al. Role of hemostatic factors on the risk of venous thrombosis in people with impaired kidney function. Circulation 2014;129(6):683–91. 3 Sardar P et al. Novel oral anticoagulants in patients with renal insufficiency: a meta- analysis of randomized trials. Can J Cardiol 2014;30(8):888–97. 4 Moss AS, Dimitropoulous G, Lip GYH. Clinical implications, benefits and pitfalls of using and reversing non-vitamin K antagonist oral anticoagulants. Expert Rev Hematol 2017;10(9): 833–45. 5 Harenberg J et al. Anticoagulation in patients with impaired renal function and with haemodialysis. Anticoagulant effects, efficacy, safety, therapeutic options. Hamostaseologie 2015;35(1): 77–83. 6 Gomez-Outes A et al. Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis. Thromb Res 2014;134(4):774–82. 7 Nielsen PB et al. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol 2015;104(5):418–