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DOAC dose adjustment in renal impairment


Review of: Inohara T, Holmes DN, Pieper K, et al. Decline in renal function and oral anticoagulation dose reduction among patients with atrial fibrillation. Heart 2020;106:358–364.

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Key learning points

  • Lower doses of direct oral anticoagulants (DOACs) are recommended when renal function falls below a particular threshold.

  • This US registry-based study assessed renal function and DOAC dosing over time.

  • Of the 4% of people treated with a DOAC who met the criteria for a dose reduction, only 20% of them had an appropriate dose adjustment.

Data from a US registry study has highlighted a lack of adherence to guidelines on direct oral anticoagulant (DOAC) dosing in people with atrial fibrillation (AF).1


This prospective registry study analysed changes in renal function over time in patients with AF.1 It also assessed whether patients required dose adjustment of DOAC treatment over the study period, and how often these dose adjustments were made. The authors analysed data from 6682 patients (57% male) enrolled between 2013 and 2016. Patients had a median age of 72 years, a median baseline creatinine clearance (CrCl) of 80 mL/min and over 90% had a CHA2DS2VASc score ≥2. A total of 5566 (83.3%) were treated with a DOAC and 1116 (16.7%) were treated with warfarin. Serum creatinine levels were collected every 6 months up to 2 years and CrCl was calculated using the Cockroft-Gault equation. Worsening renal function was defined as a decrease in CrCl of >20% from baseline at any point in the study.

Over the course of the study, CrCl declined in the DOAC group with an average reduction of 7 mL/min from baseline and 1231 (22%) had worsening renal function.1 Among the 4120 patients on standard dose DOACs at baseline, 154 (3.7%) had CrCl levels that met the threshold for dose adjustment and the DOAC dose was appropriately reduced in 31 (20%) patients. Of those patients who were eligible but did not have a dose adjustment, two people had major bleeds and three people required hospitalisation for bleeding compared with no major bleeds or hospitalisation for bleeding among patients who did have their doses appropriately reduced. One patient who had an appropriately reduced dose had a stroke or transient ischaemic attack compared with none in the other group. In 23% of patients renal function recovered sufficiently not to require a dose reduction.

One limitation of the study was that more than half of the patients were censored before 12 months follow-up because they stopped oral anticoagulant therapy, switched from warfarin to DOAC, died or were lost to follow-up.1

(The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is sponsored by Janssen Scientific Affairs.)


A DTB editorial recently highlighted that although DOACs have several advantages over warfarin, dosing needs to be carefully monitored in people with renal impairment, which is a common comorbidity in patients with AF.2 All the DOACs are dependent on the kidney for excretion and drug accumulation leading to increased anticoagulation is associated with declining renal function. A lower dose is recommended for each DOAC when renal function falls below a set level. The National Institute for Health and Care Excellence’s Clinical Knowledge Summary on oral anticoagulation recommends that renal function should be regularly assessed for patients taking DOACs.3 If renal function has declined, treatment should be reviewed as the DOAC may need to be stopped or a lower dose used. The American Heart Association recommends that for patients taking a DOAC, renal function should be regularly monitored and dose adjustments made according to national dosing guidelines.4

The registry study used the Cockcroft-Gault equation for calculating CrCl, which was the one used in the major DOAC clinical trials.1 Although the registry study included a comparatively small cohort, it used data from routine clinical practice that was more likely to reflect the older, multimorbid population commonly prescribed DOACs outside of a clinical trial setting.1 The results highlighted the need to monitor renal function regularly and to adjust DOAC doses in line with the Summary of Product Characteristics. The European Heart Rhythm Association recommends that if CrCl is ≤60 mL/min, the frequency of DOAC monitoring can be guided by dividing CrCl by 10 to obtain the minimum frequency of renal function testing in months.5



  • Contributors DTB Team.

  • Provenance and peer review Commissioned; internally peer reviewed.