SP305NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH SEVERE CHRONIC KIDNEY DISEASE, A REAL CHALLENGE

Abstract

INTRODUCTION AND AIMS: Patients with severe chronic kidney disease (CKD) usually have an increased risk for thromboembolic disease, especially associated with cardiovascular comorbidities. Furthermore, the use of anticoagulation therapy in patients with renal impairment can induce severe bleeding episodes, because the accumulation or direct interference of these substances with an already damaged coagulation system, due to the action of uremic toxins. Anticoagulants that can accumulate in patients with CKD including novel, direct oral anticoagulants (DOAC) such as rivaroxaban, apixaban, dabigatran, or edoxaban, leading to bleeding episodes. Several metaanalysis of patients with moderate CKD showed no significant differences in strokes, systemic thromboembolism, or thromboembolism-related death with DOAC, as compared to vitamin-K antagonists (VKA). Data concerning the use of DOAC in patients with severe CKD, both predialysis or dialysis, are scarce.Aimof our study was to determine the efficacy and safety of novel, direct oral anticoagulant therapy, recommended to control and help lower high risk conditions for strokes or thromboembolism, in patients with severe CKD. METHODS: The prospective study included 86 CKDpatients with eGFR< 30 ml/min/ 1.73m2, calculated using CKD-EPI equation. Our CKDpatients had indication of anticoagulant therapy for their increased risk of stroke or systemic embolism. About 90%of the patients were switched from acenocoumarol therapy, and only 10%received theDOAC as first-line anticoagulant therapy. Patients weremonitored fromthe point of view of aggravation of renal impairment underDOAC therapy.Worsening of renal function was defined as an annual decrease withmore than 25% frombaseline, in eGFR.We examined the occurrence of stroke or systemic embolism(primary outcome), as well as major bleeding (safety outcome), andmortality in relation to renal function over time. RESULTS:Among our study group of 86 patients, the median age was 62.4 years and 42% of patients were females, follow-up 1 year. Patients of our study group were using apixaban (62.8%), rivaroxaban (22%), or dabigatran (15.2%). Anticoagulant therapy in these CKDpatientswas indicated for treatment of: atrial fibrillation (52.3%), deep venous thrombosis (DVT-24.4%), and pulmonary or systemic thromboembolism(23.3%). Worsening in eGFRmore than 25% was observed in 20.9%of the patients, but not related necessary toDOACs. The risks of stroke or systemic embolismwere higher in patients with worsening renal function (HR, 1.76; 95% CI, 1.27-2.22 for stroke or systemic embolism). Major gastro-intestinal or intracranial bleedings occurred in 29% of our patients and 19.7%of patients died,mainly due to severe cardiovascular events.More than 50% of severe events occured in CKDpatients over 80 years old. CONCLUSIONS: The efficacy and safety of DOACs in our study group, as well asmortality, especially for reduced dose of apixaban, were similar with those of the studies or meta-analysis including patients with moderate CKD, but the sample size is relatively reduced, so further multicenter, population based studies are needed.