Different renal function estimation formulas for adverse outcomes in patients with atrial fibrillation receiving direct oral anticoagulants.

BACKGROUND

The Cockcroft-Gault (CG) formula remains the gold standard for renal function assessment in patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs), although various other estimation formulas exist.

OBJECTIVE

To compare the concordance and predictive performance of different renal function formulas regarding clinical outcomes in patients with AF receiving DOAC therapy.

METHODS

We retrospectively enrolled 21,318 patients with non-valvular AF receiving DOACs between June 2012 and December 2021 from a multicenter database in Taiwan. Renal function was estimated using 8 formulas: CG, CG adjusted for body surface area, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Japanese Society of Nephrology-Chronic Kidney Disease Initiatives, Full Age Spectrum, Lund-Malmö Revised, and European Kidney Function Consortium. Concordance was assessed using weighted Cohen's Kappa. Cox regression, receiver operating characteristic (ROC) curves, and Harrell's C-index were used to evaluate their associations with clinical outcomes, defined as a composite of thromboembolism, all-cause mortality, and major bleeding.

RESULTS

Most patients were classified as having normal renal function (≥60 mL/min/1.73 m2 (or mL/min) across the 8 renal function formulas, with proportions ranging from 25.7% using the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives formula to 65.3% using the CKD-EPI formula. The concordance between the CG and MDRD (K = 0.512; 95% confidence interval [CI], 0.493-0.530) or CKD-EPI (K = 0.481; 95% CI, 0.462-0.500) formula is only moderate. The risk of adverse composite outcomes increases exponentially when renal function falls below 60 mL/min/1.73 m2 (or mL/min) for the 8 formulas. Conversely, for patients with renal function values of ≥60 mL/min/1.73 m2 (or mL/min), the relationship diverged across the 8 formulas. Both the MDRD (area under the curve [AUC], 0.641; 95% CI, 0.633-0.649) and CKD-EPI (AUC, 0.664; 95% CI, 0.656-0.672) formulas, along with other renal function equations, demonstrated inferior discriminatory performance for predicting major adverse events compared with the CG formula (AUC, 0.707; 95% CI, 0.700-0.714).

CONCLUSION

The CG formula plays a crucial role in managing Asian patients with AF in the DOAC era, proving essential for both guiding dosing and predicting adverse clinical events.