Oral Anticoagulant Therapy and Renal Dysfunction: A Two-way Street?

December 6, 2017

Study net-net: Account for kidney function when dosing the direct oral anticoagulants -- but also account for an agent's potential renal harm.

Atrial fibrillation (AF) and renal dysfunction are intimately linked conditions. They share many overlapping risk factors, such as hypertension and diabetes, and have similar natural history – both tend to be chronic and progressive. In the case of AF, both the disease itself and its treatment (ie, oral anticoagulants) are linked with chronic kidney disease.

Until now, most practitioners understood this to mean that the new direct oral anticoagulants (DOACs) must be “renally dosed,” or adjusted for a patient’s glomerular filtration rate (GFR), to avoid under- or over-anticoagulation. A study published in the November 2017 issue of JACC by researchers at the Mayo Clinic, however, provides some interesting insights into the relationship between oral anticoagulants and kidney disease: it may be a two-way street. Given that patients with nonvalvular AF are usually anticoagulated for life, the consequences of these therapies for kidney function can be significant.

Three DOACs (dabigatran, rivaroxaban, apixaban) and warfarin were considered in this observational study which examined 9,769 patients over ~5.5 years and used sophisticated statistical methods to balance > 60 baseline characteristics to create a weighted population to assess risk. Multiple measures of kidney function were investigated with prespecified thresholds: ≥ 30% decline in eGFR; doubling of serum creatinine; acute kidney injury (AKI); and, kidney failure. The three DOACs were pooled and were associated with 23% to 38% lower hazard of these endpoints compared with warfarin. Individually, dabigatran and rivaroxaban were associated with lower rates of adverse renal outcomes but apixaban had no association with any of the adverse renal outcomes.

Three important take-homes from this study:

  • A significant number of patients with AF progressed to renal disease; ~1 in 4% had a ≥ 30% decline in eGFR and 1 in 7 had an episode of AKI at the end of 2 years in this study.
  • Clinicians need to consider not just renal function’s impact on the choice of drug and its dosing but also the drug choice’s impact on renal function.
  • Patients on warfarin who had a supratherapeutic INR (>3) had a much higher risk of adverse renal outcomes.

In patients with existing renal compromise, apixaban may be the drug of choice as its renal elimination is the lowest (25% to 27%) among the three DOACs. And, based on the findings of this study, dabigatran or rivaroxaban may be the best choice in patients with normal GFR who remain at risk for progression to CKD because both drugs appear to pose a lower risk of adverse renal outcomes than apixaban.

In neither population does warfarin appear to be the optimal choice. Are you surprised?

Source: Yao X, Tangri N, Bersh BJ, et al. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2017;70:2621-2632; DOI: 10.1016/j.jacc.2017.09.1087.