Position paper on the safety/efficacy profile of Direct Oral Anticoagulants in patients with Chronic Kidney Disease: Consensus document of Societ\xe0 Italiana di Nefrologia (SIN), Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA) and Societ\xe0 Italiana per lo Studio dell\u2019Emostasi e della Trombosi (SISET)

Giuliano Brunori,Daniela Poli,Doris Barcellona,Elvira Grandone,Simonetta Genovesi,Giacomo Forneris,Paolo Gresele,Armando Tripodi,Marco Marietta,Filippo Aucella,Sophie Testa

doi:10.1007/s40620-020-00768-3

Abstract

Direct oral anticoagulants (DOAC) are mostly prescribed to prevent cardioembolic stroke in patients with non-valvular atrial fibrillation (AF). An increasing number of guidelines recommend DOAC in AF patients with preserved renal function for the prevention of thromboembolism and an increased use of DOAC in daily practice is recorded also in elderly patients. Aging is associated with a reduction of glomerular filtration rate and impaired renal function, regardless of the cause, increases the risk of bleeding. Multiple medication use (polypharmacy) for treating superimposed co-morbidities is common in both elderly and chronic kidney disease (CKD) patients and drug-drug interaction may cause accumulation of DOAC, thereby increasing the risk of bleeding. There is uncertainty on the safety profile of DOAC in patients with CKD, particularly in those with severely impaired renal function or end stage renal disease, due to the heterogeneity of studies and the relative paucity of data. This document reports the position of three Italian scientific societies engaged in the management of patients with atrial fibrillation who are treated with DOAC and present with CKD.

Highlights

Vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC) are widely prescribed for non-valvular atrial fibrillation (AF) and treatment/prophylaxis of venous thromboembolism
Polypharmacy is frequent in elderly individuals because of the presence of several co-morbidities and many important interactions between several drugs and VKA or DOAC have been reported
Except for dabigatran, which is removed by 50–60% with a single dialysis session, other DOAC are difficult to dialyze due to their high binding to plasma proteins [4]

Summary

Introduction

Vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC) are widely prescribed for non-valvular atrial fibrillation (AF) and treatment/prophylaxis of venous thromboembolism. FDA allows the prescription of rivaroxaban (15 mg/day) and apixaban (5 mg twice a day) in patients with ESRD or undergoing dialysis if the body weight is > 60 kg or age < 80 years, whereas the European Medicines Agency (EMA) contraindicates the use of any DOAC in patients with CKD stage G4–G5. A Cochrane review reported that DOAC could be more effective than warfarin (moderate certainty evidence) in reducing the incidence of stroke and systemic embolism (five studies, 12,545 patients: RR 0.81, 95% CI 0.65–1.00) and major bleeding events (five studies, 12,521 patients: RR 0.79, 95% CI 0.59–1.04; low certainty evidence) These data were obtained mainly in patients (n = 12,155) with G3b stage, as the group of G4 stage consisted of only 390 patients [22].

Limitations

Findings

Compliance with ethical standards