It is well established that, patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are at increased risk for both thrombotic and bleeding events. Thus, long-term oral anticoagulation (OAC) treatment is strongly suggested, to reduce thromboembolic risk and cardiovascular mortality. Increased extra-coronary calcifications, deterioration of renal function in pre-reduced estimated glomerular filtration rate (eGFR), and lower rates of compliance with vitamin K antagonist (VKA) treatment led to the design of studies that compared VKAs to direct oral anticoagulants (DOACs), regarding their impact on renal function. In two large-scale registries, GARFIELD-AF1 and PREFER2, the percentage of patients with moderate-to-severe CKD was rather low, 10.9% and 13.1% respectively. XARENO was a multicentre, prospective observational study that addressed this issue, enrolling patients diagnosed with AF, receiving at least 3 months’ treatment with VKAs or rivaroxaban, prior to enrolment, moderate-to-severe CKD, indicated by eGFR 15-49ml/min/1.37m2, and were followed up for at least 12 months. The primary endpoint was the absolute change in eGFR3.
Out of 1,455 enrolled, 764 patients were in the rivaroxaban arm, while 691 patients were in the VKA arm. Regarding thrombotic and hemorrhagic risk, median CHA2-DS2-VASc was 4 and median HAS-BLED 2, in both arms (4). In the intention-to-treat analysis, Kreutz et al. demonstrated that rivaroxaban was associated with significant reductions in adverse renal outcomes; specifically, 38% hazard reduction for the composite of any adverse renal outcome and a 49% reduction in the hazard of renal decline to an eGFR <15. Moreover, it is key that there was a significant decrease in all-cause mortality in the rivaroxaban arm, compared to VKA (HR: 0.76). Finally, rivaroxaban was associated with 24% less treatment discontinuation.
XARENO was not powered to show any benefit in thrombotic and bleeding endpoints, and was not designed as a randomised clinical trial; however, renal outcomes are enhanced when rivaroxaban is the acting agent in real world data, consistent with other registries, even in lower eGFR and more frail situations. In terms of thrombotic risk, not only renal outcomes, but also the composite clinical outcomes were consistent with ROCKET-AF trial (5). Recently, a patient-level network meta-analysis comparing DOACs vs VKAs regarding their safety and efficacy characteristics, across continuous creatinine clearance levels (6), showed that even in low eGFR (CKD stage III, IV), standard-dose DOACs are at the same time safer and more effective, compared to VKAs. Most importantly, lower-dose DOACs do harm, as they do not decrease bleeding events and are associated with increased thromboembolic risk. Thus, in consistency with XARENO’s real world data, this meta-analysis highlights the demanding need for DOAC utilisation and at the optimal, standard dose, in patients with deteriorated renal function.
Our mission: To reduce the burden of cardiovascular disease.