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Patients with atrial fibrillation (AF) and renal impairment require dose reductions of non-vitamin K antagonist oral anticoagulants (NOACs).
But researchers found that 43% of these patients were potentially overdosed, and as many as 1 in 6 (13%) without renal impairment are potentially under dosed.
Failing to reduce the dose for patients with kidney disease increases their risk of bleeding, while under dosing patients without kidney disease puts them at greater risk of stroke. These inappropriate prescribing patterns may impact patient safety without providing benefit in effectiveness.
Using a large US database of de-identified, linked clinical and administrative claims information, the research team found 14,865 patients with AF who were prescribed apixaban, dabigatran, or rivaroxaban between October 1, 2020, and September 30, 2015. Of these, 1,473 had renal impairment.
All three drugs have a standard dose for most patients and a lower dose for patients with kidney issues. And their analysis revealed that 16% percent of all patients received a dose inconsistent with US Food and Drug Administration labeling.
The research team published its findings in the Journal of the American College of Cardiology.
“We conducted this study to highlight the prevalence of inappropriate dosing in routine clinical practice and the associated adverse outcomes,” said Peter Noseworthy, MD, of the Mayo Clinic in Rochester, Minnesota, and senior author of the paper.
“This study underscores the importance for physicians to be vigilant of kidney function when selecting or adjusting dose.”
Dr Noseworthy explained that overdosing is a fairly straightforward problem that can be avoided by regularly monitoring kidney function.
In the kidney-impaired patients who were potentially overdosed, the hazard ratio for the risk of major bleeding was 2.19 (95% confidence interval: 1.07 to 4.46). There was no statistically significant difference in stroke with the 3 NOACs pooled.
However, under dosing is more complex because a balance needs to be established between stroke reduction and bleeding risk, Dr Noseworthy pointed out.
Among the 13,392 patients without renal impairment and no indication for dose reduction, the hazard ratio for a higher risk of stroke was 4.87 (95% confidence interval: 1.30 to 18.26). There was no statistically significant difference in major bleeding in apixaban-treated patients nor statistically significant relationships in dabigatran- or rivaroxaban-treated patients without renal impairment.
“I think physicians often choose to reduce the dose,” Dr Noseworthy explained, “when they anticipate their patients are at a particularly high bleeding risk—independent of kidney function.”
“Dosing errors of these blood-thinning medications in patients with atrial fibrillation are common and have concerning adverse outcomes,” said Xiaoxi Yao, PhD, also of the Mayo Clinic in Rochester, Minnesota, and lead author of the paper.
Dr Yao noted that the number of patients using these drugs has increased since their introduction in 2010. Before that, the standard blood-thinning drug was warfarin, which requires constant monitoring and doctor visits.
