A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease

Abstract

Background Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis. Methods We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included. Results Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42–1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45–0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile. Conclusion Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.

UK prescribing practice of anticoagulants in patients with chronic kidney disease: a nephrology and haematology-based survey

“…For patients with CKD stage 5 and on dialysis, most respondents would use VKAs which is likely due to a lack of licensing and limited published evidence for DOACs in this scenario. Apixaban was the DOAC selected by all respondents when used in CKD stage 5 and dialysis and this may be based on the findings of a number of observational studies and a recent systematic review from our group which showed apixaban had a lower risk of bleeding compared to warfarin [9,[39][40][41][42][43][44]. However, more evidence is needed to support the use of DOACs in the treatment of VTE in patients with CKD stage 5 and dialysis.…”

“…One in ten respondents did not use any risk scores and this may relate to their lack of validation in patients with advanced CKD [50,51]. Respondents were less likely to anticoagulate patients on dialysis which may relate to the uncertainty in whether anticoagulation reduces the risk of stroke in this group [9,52]. The use of anticoagulants versus no anticoagulation in dialysis patients with AF is currently being investigated in a number of RCTs [53][54][55].…”

“…Thromboembolic events with AF can be reduced with the prescription of oral anticoagulants, which includes the vitamin K antagonists (VKAs) and direct oral acting anticoagulants (DOACs) [8]. However, the benefits of these agents are uncertain in advanced CKD due to an associated increased risk of bleeding [9], related to uraemia-induced platelet dysfunction and an increase in gastric angiodysplasias [10,11].…”

UK prescribing practice of anticoagulants in patients with chronic kidney disease: A nephrology and haematology-based survey

“…For patients with CKD stage 5 and on dialysis, most respondents would use VKAs which is likely due to a lack of licensing and limited published evidence for DOACs in this scenario. Apixaban was the DOAC selected by all respondents when used in CKD stage 5 and dialysis and this may be based on the ndings of a number of observational studies and a recent systematic review from our group which showed apixaban had a lower risk of bleeding compared to warfarin (9,(39)(40)(41)(42)(43)(44). However, more evidence is needed to support the use of DOACs in the treatment of VTE in patients with CKD stage 5 and dialysis.…”

“…Thromboembolic events with AF can be reduced with the prescription of oral anticoagulants, which includes the vitamin K antagonists (VKAs) and direct oral acting anticoagulants (DOACs)(8). However, the bene ts of these agents are uncertain in advanced CKD due to an associated increased risk of bleeding (9), related to uraemia-induced platelet dysfunction and an increase in gastric angiodysplasias (10,11).…”