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 decisionmaking 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
Dose reductions by 30 – 50 % and / or monitoring of anti-factor- Xa activity are suggested in patients with GFR between 30 and 15ml / min
60mg in mRI . None of the factor Xa inhibitors were eliminated to a relevant degree by dialysis . Overall there may be a benefit for oral anticoagulation with anti-factor Xa DOACs compared with warfarin in patients with sRI or ESRD . Thus the door has been opened to a cautious application of these DOACs in patients with severe CKD . While data from prospective trials are lacking , we recommend monitoring of the anticoagulant effect by measuring drug-calibrated anti-factor Xa activity – by determination of trough concentrations , for the first time after three doses – if DOACs are used in patients with GFR < 30ml / min .
Conclusions CKD continues to be a major contributory factor for morbidity and mortality in the context of VTE . Anticoagulation is effective in preventing and treating thromboembolisms . The available body of evidence convincingly demonstrates that treatment with parenteral or oral anticoagulant drugs is not only effective and safe in patients with normal renal function , but also in those with slightly or moderately reduced renal function . In patients with sRI or ESRD , anticoagulant treatment for acute VTEs is challenging because prospective randomised trials , evaluating efficacy and safety in these more advanced stages of renal insufficiency are lacking . Some evidence from retrospective analyses and small prospective Phase II studies support the use of anticoagulant drugs in patients with acute VTE and sRI . In patients undergoing CHD , the benefits and harms of prolonged or long-term anticoagulation therapy are less clearly balanced .
Whereas a short-term therapeutic anticoagulation therapy for an acute VTE is recommended , the decision to proceed to a prolonged therapeutic anticoagulation needs to be critically evaluated individually in the context of the thromboembolic and haemorrhagic risks . Despite the long-standing clinical practice of using UFH and VKA in patients with ESRD , available but limited data are in favor of the use of LMWH instead of UFH . When long-term anticoagulation is indicated for VTE anti-factor Xa DOAKs may be the better choice as compared to VKA . There is a high clinical need for prospective randomised clinical trials evaluating anticoagulation strategies in patients with sRI and ESRD .
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