MO496PRESCRIPTION OF DIRECT ORAL ANTICOAGULANTS TO PATIENTS WITH MODERATE TO ADVANCED CKD : TOO LITTLE OR JUST RIGHT?
Authors: Liabeuf Sophie , Laville Solène M , Bieber Brian , Tu Charlotte , Stengel Benedicte , Wong Michelle , Calice-Siva Viviane , Fliser Danilo , Robinson Bruce , Pecoits-Filho Roberto , Massy Ziad 
Published: May 2021

Abstract

Background and Aims
Prescription of anticoagulants in patients with chronic kidney disease (CKD) is challenging, since these patients are at high risk of thromboembolic episodes, but are also prone to bleeding events. Based on a number of pivotal trials, four direct oral anticoagulants (DOACs) have been approved for use in non-valvular atrial fibrillation (AF) since 2010. These DOACs have now supplanted vitamin K antagonists (VKAs) as first-line treatment in non-CKD patients. Following post-hoc analyses of randomized clinical trials of DOACs in CKD patients performed between 2011 and 2016, a 2018 Kidney Disease Improving Global Outcomes Controversies Conference stated that although there is not enough evidence to recommend DOACs in patients with advanced CKD, these medications are safer than VKAs and not inferior for stroke preventing in patients with AF and an estimated glomerular filtration rate (eGFR) between 30 and 50 ml/min/1.73 m2. Here, in a study of stage 3 to 5 CKD patients, we sought to describe multinational prescription patterns for oral anticoagulants in general and for VKAs vs. DOACs in particular.

Method
We analyzed data from the international CKD Outcomes and Practice Patterns Study (CKDopps) of non-dialysis CKD patients ≥ 18 years of age with an eGFR &lt;60 mL/min/1.73 m² at study enrollment. Participants were selected from national samples of nephrologist-run CKD clinics in Brazil, France, Germany, and the USA between January 2013 and April 2019. The CKDopps is ongoing, and at least 3 years (for the USA, Germany, and Brazil) or 5 years (for France) of prospective follow-up are planned. We assessed prescription patterns for oral anticoagulants regardless of indication at baseline and during follow-up.

Results
Of the 8154 patients enrolled, 7092 had drug prescriptions data available at baseline, and 1080 (15%) of these had at least one prescription of an oral anticoagulant. At baseline, VKAs were the most frequently prescribed oral anticoagulants (n=984, 91%), and only 97 of the 1080 patients (9%) were on DOACs (91 on a direct factor Xa inhibitor and 6 on a direct thrombin inhibitor). This low DOAC prescription rate was observed in France, the USA, Brazil and Germany. There was an upward trend in DOAC prescription (relative to VKAs) over the course of the study. Over a median [interquartile range] follow-up period of 3 years [1.5-4.5], 287 incident oral anticoagulant prescriptions were reported, 177 started on VKAs and 110 started on DOACs. Among the patients receiving a VKA at baseline, only 44 switched to a DOAC.

Conclusion
In an international sample of non-dialysis CKD patients (eGFR &lt;60 mL/min/1.73 m²), we observed low prescription of direct oral anticoagulants (9%) at baseline, relative to vitamin K antagonists (91%) across countries included in the analysis. However, there was an upward trend in DOAC prescriptions (relative to VKAs) over the course of the study. In view of the risk of significant adverse events associated with VKAs, the prescription of DOACs should be encouraged - particularly for CKD stage 3 patients and future studies of risk/benefit comparing VKAs and DOACs are necessary in CKD patients.