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.

Keywords: Anticoagulation; Atrial fibrillation; CKD; Stroke; Thrombosis.

Fig. 1

Flow diagram of study selection

Fig. 2

Recurrent VTE events from RCTs in patients with CrCl 30-50 ml/min [–19]. Figure created using RevMan software [23]. Please note the number of patients from Agnelli 2013 in this analysis differs from the total number of patients in Table 1. The numbers are taken directly from the paper and it is assumed the difference relates to missing outcome data or loss of follow up [18]

Fig. 3

Major bleeding events from RCTs in patients with CrCl 30-50 ml/min [–19]. Note that the Buller study is a composite outcome of major bleeding and CRNMB. Figure created using RevMan software [23]. Please note the number of patients from Bauersachs 2014 and Goldhaber 2017 in this analysis differs from the total included patients in Table 1. The numbers are taken directly from the papers and it is assumed the difference relates to missing outcome data or loss of follow up [16, 19]

Fig. 4

Stroke reported from RCTs in patients with AF and CrCl < 50 ml/min. Figure created using RevMan software [23]

Fig. 5

Major bleeding from RCTs in patients with AF and CrCl < 50 ml/min. Figure created using RevMan software [23]

Fig. 6

Authors suggested use of DOACs in patients with acute VTE depending on renal function

Fig. 7

Authors suggested use of DOACs in patients with AF depending on renal function