Safety and efficacy of rivaroxaban compared to warfarin in patients with atrial fibrillation and advanced stages of chronic kidney disease

Abstract

Background Atrial fibrillation (AF) is a common comorbidity in around 10–15% of patients (pts) with CKD, while 30% of those with AF have CKD. In pts with advanced stages of CKD, safety and efficacy profiles of novel oral anticoagulants, in particular rivaroxaban, have been understudied. Purpose To evaluate safety and efficacy of rivaroxaban in pts with stage 4 CKD or a transient reduction in glomerular filtration rate (GFR) to 15–29 ml/min/1.73 m2. Materials and methods Data of 3,500 pts with nonvalvular AF in cardiovascular units for the period from 2017 to 2019 were analyzed. Of these, 507 (15%) showed a decrease in GFR to 29–15 ml/min/1.73 m2. 109 (3.1%) pts enrolled in the study (in accordance with inclusion criteria) and were randomized in a 2: 1 fashion to either the 15 mg rivaroxaban (n=74) or warfarin (n=36) group. The pts had either not previously been taking anticoagulants, or TTR was <65% in the case of taking warfarin. The average follow-up period was 18 months. Visits took place every 3 months, when compliance, haemoglobin were checked and GFR calculation was carried out. Primary endpoint: development of major and minor bleeding on the BARC scale. Secondary endpoints: thromboembolic events, cardiovascular mortality and all-cause mortality. Results The pts were of similar clinical and demographic profile. The median age was 77 years with 32 men in the rivaroxaban group and 14 in the warfarin group. The average CHA2DS2-VASc score was 4.6 and 4.7 (n/s) in the rivaroxaban and warfarin group, respectively, while the average HAS-BLED score was 3 (n/s) in both. Pts taking warfarin were significantly more likely to develop minor bleedings: 26 (72%) vs 27 (37%) in the rivaroxaban group, p=0.001. There were not detected significant differences in the ratio of major bleedings (warfarin 3 (8.3%) versus rivaroxaban 2 (2.7%) cases, p=0.3). No significant differences at secondary endpoints were observed. In the warfarin group, 1 (2.8%) ischemic stroke and 1 fatal haemorrhagic stroke occurred. In the rivaroxaban group, 1 (1.4%) ischemic stroke occurred during a 5-day break in taking the anticoagulant. 5 (6.9%) pts in the rivaroxaban group developed ACS, vs 1 (2.8%) in the warfarin group (n/s). 2 (2.7%) pts died from myocardial infarction in the rivaroxaban group and 1 (2.8%) - in the warfarin group (n/s). Mortality from all causes was 5 (6.6%) in the rivaroxaban group and 3 (8.3%) in the warfarin group (n/s). In the rivaroxaban group, GFR (CG formula) improved significantly more since the 3rd month of observation (in the 18th month of observation, the median value was 35.0 [29.0; 39.5] ml/min/1.73 m2 vs 27.0 [21.5; 31.5] ml/min/1.73 m2 in the warfarin group, p<0.001). Conclusion Significantly more pts within the warfarin group had minor bleedings. Pts during warfarin and rivaroxaban therapy showed an improvement in glomerular filtration, which was more pronounced in the rivaroxaban group. Funding Acknowledgement Type of funding source: None

Potential for anticoagulant therapy in the most vulnerable groups of patients

“…Комплексный взгляд на риски данной группы больных диктует обратить внимание на результаты РКИ Chashkina M, et al [35]. В него включались пожилые и очень пожилые (средний возраст составил 77 лет) пациенты с ФП и ХБП 4 стадии или выявленным впервые при госпитализации транзиторным снижением скорости клубочковой фильтрации до 15-29 мл/мин/1,73 м 2 , сохраняющемся в течение всего стационарного периода.…”

“…И даже у пациентов с выраженным снижением почечной функции -с ФП и ХБП 4 стадии в уже упомянутом выше РКИ Chashkina M, et al (сред-ний бал по шкале HAS-BLED составил 3,0 в группе риваро ксабана и 3,1 в группе варфарина, так же у 46% и 50% пациентов, соответственно, была анемия) терапия ривароксабаном сопровождалась значимо меньшим числом геморрагических осложнений в сравнении с варфарином: как больших и клинически значимых небольших кровотечений по ISTH (10,9% в группе ривароксабана и 27,7% в группе варфарина, р=0,03), так и малых кровотечений по ISTH (36,9% и 61,1%, соответственно, р=0,01). Важно отметить, что почти половина пациентов в этом исследовании имели анемию (ФР кровотечений), и ривароксабан продемонстрировал высокий профиль безопасности и у этой группы пациентов [35].…”

Frequency of Major Bleeding Episodes With Rivaroxaban for Atrial Fibrillation Related Stroke Prevention in Chronic Kidney Disease Patients

“…2 Atrial fibrillation (AF) is a common comorbidity with chronic kidney disease (CKD) (10-15%) while 30% of those with AF has CKD. 3 Among patients of AF with moderate to high risk of stroke on anticoagulation, those with persistent AF have a higher risk of thromboembolism and worse survival compared with paroxysmal AF. 4 The risk of stroke is similar in patients with or without valvular disease.…”