Older adults taking levothyroxine at higher doses may be at an increased risk of developing atrial fibrillation (AF) compared to patients taking lower doses, according to the findings of a population-based observational study.

To evaluate the association between cumulative levothyroxine exposure and risk of AF and ischemic stroke in older patients, the study authors utilized healthcare databases from Ontario, Canada to identify adults 66 years of age and older with no history of AF who filled at least 1 prescription for levothyroxine between April 1, 2007, and March 31, 2016. Cases, which were defined as patients who had incident AF (hospitalization or emergency room visit) between the date of their first prescription and December 31, 2017, were matched with up to 5 controls that did not have AF on the same index date. The index date was defined as the date of AF.

“Cumulative levothyroxine exposure was estimated based on total milligrams (mg) of levothyroxine dispensed in the year prior to index date,” the authors explained. They added, “Using nested case-control approach, we compared outcomes between older adults who received high (≥0.125mg/day), medium (0.075-0.125mg/day), or low (0-0.075mg/day) cumulative levothyroxine dose.” Outcomes were compared between current, recent past, and remote past use of levothyroxine. The secondary outcome of the analysis was ischemic stroke.

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The study authors reported that 16.1% of older patients that were identified as taking levothyroxine in their analysis had an episode of AF (30,560/189,672).  Findings of the study revealed that, after adjusting for covariates, high cumulative levothyroxine exposure significantly increased the risk of AF compared to low levothyroxine exposure (adjusted odds ratio [aOR], 1.29; 95% CI, 1.23-1.35; P <.0001). Similarly, medium cumulative exposure was associated with an increased risk of AF (aOR, 1.08; 95% CI, 1.04-1.11; P <.0001).

Conversely, data analysis revealed that there was no association between exposure to levothyroxine and ischemic stroke. Findings of the study also showed remote levothyroxine use to be associated with lower risks of AF (aOR, 0.56; 95% CI, 0.52-0.59; P <.0001) and ischemic stroke (aOR, 0.61; 95% CI, 0.56-0.67; P <.0001) compared with current use of levothyroxine.

“In our study of over 180,000 older adults treated with levothyroxine, we demonstrate that increased cumulative exposure to levothyroxine dose over 1 year was associated with higher risk of incident AF in a dose-response fashion,” the authors stated. The risk of AF was found to begin increasing at an average dose of 0.075mg of levothyroxine daily, with the highest risk occurring in patients taking greater than 0.125mg daily.

“These findings highlight a need to consider more conservative doses with closer monitoring, and further research to direct appropriate treatment targets in older persons,” the authors concluded.


Gong IY, Atzema CL, Lega IC, et al. Levothyroxine dose and risk of atrial fibrillation: a nested case-control study. American Heart Journal (2020). doi: 10.1016/j.ahj.2020.09.016.

This article originally appeared on MPR