The use of direct oral anticoagulants in chronic kidney disease

Abstract

Increasing use of direct oral anticoagulants (DOACs) has made management of non-valvular atrial fibrillation and venous thromboembolism easier in most patients. But the presence of co-existing renal impairment could render the use of DOACs problematic because all of these drugs have varying degrees of renal excretion. In this paper we address misconceptions about the safety and efficacy of DOACs in moderate-severe renal impairment by presenting a summary of the literature from phase III trials and real-world studies. It also addresses the important consideration of correct estimate of renal function for DOAC dosing. It is hoped that the review will serve as a valuable resource for clinicians involved in anticoagulation decision-making in patients with renal impairment to guide the choice of most suitable agent. Accurate dosing is of particular relevance as registry data suggests it is done inconsistently and may be resulting in avoidable thromboembolic and bleeding events.

Role of direct oral anticoagulants in patients with kidney disease

“…Br J Haematol. 2018;183:170-184, 45 of DOACs in patients with type 2 diabetes demonstrated no differences in 2-hour pharmacokinetics or pharmacodynamics compared with nondiabetic controls for rivaroxaban, apixaban, or dabigatran. 60 Data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial demonstrated similar benefits for both diabetic and nondiabetic participants, suggesting diabetes itself did not influence efficacy.…”

“…Below, we describe common causes of kidney disease and particular scenarios that might warrant anticoagulation ( Table 2). 45 Nephrotic syndrome VTE is a well-recognized nephrotic syndrome (NS) complication. [46][47][48] In the aforementioned Danish registry, adult patients with NS had the highest risk of VTE (odds ratio, 2.17; 95% confidence interval [CI], 1.68-2.80).…”

“…Dose adjustments are required for reduced CrCl and based on anticoagulant indication and regulatory agency (i.e., Food and Drug Administration vs. European Medicines Agency) ( Table 2). 45 A prescription data analysis showed that 28% of patients with CKD prescribed DOACs did not receive recommended dose reductions. 107 Notably, all pivotal phase 3 DOAC trials used CrCl determined using the Cockcroft-Gault formula to estimate kidney function rather than eGFR and excluded patients with CrCl <25 to 30 ml/min.…”

Increased Incident Ischemic Stroke Risk in Advanced Kidney Disease: A Large-Scale Real-World Data Study

“…The present study was a retrospective cohort study and indication bias or other uncontrolled factors, such as activities of daily living, might contribute to the conflicting findings. Regarding the type of OAC, we revealed that the risk for IS/SE was equivalent between VKA and DOAC, and the bleeding rate with VKA use tended to be higher than that with DOAC use; thus, DOAC is preferable for AF with kidney disease because of its safety profile [22,35]. The reason for kidney disease being a risk factor for IS/SE is owing to a structural problem, such as vascular wall calcification, or a serological problem, such as increased plasminogen activator inhibitor 1 [36], von Willebrand factor [37], increase and activation of coagulation factors [38], or increased inflammatory substances [39].…”

“…Nevertheless, it is inappropriate to use OAC in people with AF and kidney disease [19] owing to a high risk of bleeding [20]. Some novel OAC, referred to as direct oral anticoagulants (DOACs), are mainly excreted by the kidney; thus, dose adjustment is needed in people with kidney disease [21,22]. Furthermore, kidney disease is risk factor for bleeding [23][24][25].…”