Apixaban Vs Vitamin K Antagonist As Anticoagulant Therapy in Patients with End-Stage Kidney Disease on Hemodialysis and with Atrial Fibrillation

Abstract

BACKGROUND Evidence of net safety and benefit of anticoagulation for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF) is lacking because patients with advanced CKD and those with end-stage kidney disease (ESKD) have been excluded from randomized clinical trials of stroke prevention in AF. In Europe, apixaban is not approved for the indication of prevention of stroke and systemic embolism in adult patients with ESKD on hemodialysis and AF. AIM To assess the effectiveness and safety according to Apixaban or VKA treatment. The effectiveness outcome was defined by ischemic stroke, all-cause death and myocardial infarction. The safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. METHODS Unicenter, observational and retrospective study. Data was collected between January 2018 and July 2022. We included adult patients with ESKD on hemodialysis and AF and a CHA2DS2-VASc score ≥2 treated with low dose of Apixaban (2.5 mg twice daily) or VKA from the beginning of treatment. Patients in the VKA group received Acenocoumarol. Demographic, laboratory data and clinical presentation of AF were collected. Patients had a minimum follow-up (FU) of 6 months. Apixaban plasma drug concentrations were measured during the FU (week 1 and month 3). Blood samples were draw just before the next dose (Ctrough) and at 2-3 hours (Cpeak) after of drug intake using the Technoclone anti-Xa assay from Technoclone (Vienna-Austria). Bleeding events were classified according to ISTH criteria. RESULTS A total of 302 patients with NVAF and ESKD on hemodialysis were included. Among all patients, 192 (63.5%) were treated with Apixaban and 110 VKA. Mean FU was 14.8 and 12.5 months (DOAC vs VKA; p:0.53). Demographic characteristics are summarised in table 1. In Apixaban group, 100% of patients received reduce-dose, according to the care protocol established in our center and showed predictable pharmacokinetic, Ctrough (94.5- 180 μg/L) and Cmax (150-419 μg/L). In VKA group, Time in therapeutic range (international normalized ratio, 2.0-3.0) for Acenocumarol treated patients was 42% (interquartile range, 19%-60%). Stroke or systemic embolism occurred in three patients in the Apixaban group (1.04 %/year) and seven patients in the VKA group (7.2 %/year) [DOAC vs LMWH; p<0.05]. The apixaban group experienced fewer overall bleeding events than the VKA group (17.3% vs 39.7%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.13; 95% CI = 0.04-0.42; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on VKA (4.7% vs 25%; P = .01). There were no significant differences regarding in all-cause mortality, 18.8% versus 21.5% respectively. CONCLUSIONS Compared to VKA, our findings suggest that low dose of apixaban is a safe and effective alternative in patients with AF and ESKD on hemodialysisis and low dose of apixaban showed predictable pharmacokinetic.