Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review

ABSTRACT

Introduction

Direct oral anticoagulants (DOACs) are widely prescribed nowadays. Available DOACs are renally eliminated to some extent and need dose adjustment in patients with kidney dysfunction. Cockcroft-Gault (CG) formula has been used to estimate creatinine clearance in DOACs trials. Nowadays, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are preferred equations for estimating glomerular filtration rate (GFR). We reviewed studies that simulated DOACs dosing in patients with atrial fibrillation by MDRD, CKD-EPI, and CG.

Areas covered

DOACs dose discordance varies from 28.8% underdosing to 59.2% overdosing when MDRD or CKD-EPI equations are substituted for CG. MDRD and CKD-EPI overestimate the GFR in lower thresholds of kidney function especially in elderly and females and result in overestimation of DOACs dosing or misclassifying the patients to be eligible for receiving DOACs when they are contraindicated. Compared with CG, MDRD and CKD-EPI underestimate the level of kidney function in higher GFR extremes and in these patients suggest DOACs when they are not recommended or suggest lower doses.

Expert opinion

Until running large clinical studies on efficacy/safety of DOACs dosing using MDRD or CKD-EPI equations, use of CG method for DOACs dosing is recommended in real practice.

KEYWORDS:

• Cockcroft-Gault
• CKD-EPI
• direct oral anticoagulants
• DOACs
• dose adjustment
• glomerular filtration rate
• MDRD

Article highlights

• Nonvalvular atrial fibrillation (AF), the most common type of arrhythmia among adults, puts the patients in stroke risk. AF prevalence increases in patients with chronic kidney disease. In addition, renal dysfunction increases the risk of thromboembolism and stroke.

• Oral anticoagulants are the mainstay of AF treatment to prevent thromboembolic events. They are also used to treat some other thromboembolic events.

• Warfarin, the traditional oral anticoagulant, has been mostly substituted with DOACs in past years because of the favorable efficacy and safety profile.

• All DOACs are eliminated by kidney to some extent and need dose adjustment in patients with chronic kidney disease.

• Cockcroft-Gault (CG) formula that employs actual body weight has been applied in DOACs clinical trials for estimating the level of kidney function and dose adjustment.

• In general, MDRD and CKD-EPI equations compared with CG, overestimate the level of kidney function in patients with moderate to severe chronic kidney disease especially in elderlies and females; therefore, using these newer formulas for DOAC dose adjustment may put the patient in the risk of drug overdose and bleeding.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.