Over the coming decades, a growing number of Americans are expected to develop atrial fibrillation, a common heart condition characterized by an irregular and often rapid heart rate. The Centers for Disease Control and Prevention estimates that between 2.7 and 6.1 million Americans are living with the condition, which is also associated with a fivefold greater risk of stroke.
But almost 1 in 6 of the millions of Americans on new blood-thinning medications for atrial fibrillation may not be receiving the recommended dose, Mayo Clinic research finds.
Roughly 10 percent of patients on these drugs have severe kidney disease, and the research, published June 5 in the Journal of the American College of Cardiology, found that more than 40 percent of them are receiving a higher dose than recommended. That could lead to serious bleeding risks.
Also, among the 90 percent of patients without severe kidney disease, 13 percent may be underdosed. The researchers found that for one medication in the group – apixaban – underdosing may be less effective at preventing strokes.
“Dosing errors of these blood-thinning medications in patients with atrial fibrillation are common and have concerning adverse outcomes,” says Xiaoxi Yao, Ph.D., a health sciences researcher at Mayo Clinic and the paper’s lead author.
The paper looked at 14,865 patients from October 2010 to September 2015 on the blood-thinning drugs apixaban, dabigatran or rivaroxaban for atrial fibrillation. All three medications have a standard dose for most patients and a lower dose for patients with kidney issues. Blood-thinners are recommended for up to 90 percent of patients with atrial fibrillation as lifelong therapy.
“The number of patients using these drugs has quickly increased since the introduction of this new class of drugs in 2010,” says Dr. Yao. Before that, the standard blood-thinning drug since the 1950s was warfarin, which requires constant monitoring and doctor visits.
Using the OptumLabs Data Warehouse, a database of de-identified, linked clinical and administrative claims information, the study found that 16 percent of the patients received a dose inconsistent with U.S. Food and Drug Administration labeling. Among the patients with severe kidney impairment, 43 percent received the standard dose ─ a potential overdose. Overdosing was associated with a higher risk of major bleeding but no significant difference in stroke prevention.
Among patients without severe kidney disease, 13 percent got the lower dose ─ a potential underdose. The lower dose was associated with a higher risk of stroke but no difference for bleeding risks for apixaban users. There wasn’t a significant relationship between underdosing and the risks of stroke or bleeding for dabigatran or rivaroxaban users.
“We conducted this study to highlight the prevalence of inappropriate dosing in routine clinical practice and the associated adverse outcomes,” says Peter Noseworthy, M.D., a Mayo Clinic cardiologist and the paper’s senior author. “This study underscores the importance for physicians to be vigilant of kidney function when selecting or adjusting dose.”
Blood-thinning medication dosing is complex, and there are many factors health care providers consider when prescribing the drugs. They have to weigh the benefits and harms, and account for possible drug interactions, among other concerns.
The researchers also note that, because these blood-thinners are preventive, health care providers can’t be certain the medication prevented a stroke, but they can link bleeding events to the drugs. This could cause some providers to be cautious and prescribe a lower dose.
“Overdosing is a fairly straightforward problem and can be avoided by regularly monitoring kidney function,” says Dr. Noseworthy. “However, underdosing is more complex. These medications need to strike a balance between stroke reduction and risk of bleeding. I think physicians often choose to reduce the dose when they anticipate their patients are at a particularly high bleeding risk ─ independent of kidney function.”
For the patients’ part, they should ensure health care providers have updated medical history information and a current list of medications, especially if they see multiple providers at different hospitals or clinics.
“Physicians will also need to regularly follow up with patients on these medications to detect change in kidney function and adapt the dose accordingly,” says Dr. Yao.
The findings are a collaboration between Mayo Clinic physicians and researchers in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The teamwork ensures the research questions address unmet patient needs and places the findings in a perspective that can improve clinical practice.
Additional research team members ─ all from Mayo Clinic ─ are:
A version of this post originally appeared on the Mayo Clinic News Network.