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Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine
Wook Yi1, Bo Hyun Kim1, Mijin Kim1
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
Insights
Combination therapy with liothyronine (LT3) and levothyroxine (LT4) may increase risks of heart failure and stroke, particularly in thyroid cancer patients with long-term LT3 use. Further research is needed to confirm these findings in diverse populations.
Area of Science:
- Endocrinology
- Pharmacovigilance
- Clinical Research
Background:
- Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is prescribed for persistent hypothyroid symptoms and in thyroid cancer patients undergoing radioactive iodine therapy.
- The long-term safety of LT3, especially in Asian populations, remains controversial due to limited evidence.
- This study aimed to assess the long-term safety of LT3 therapy using a large-scale healthcare database.
Purpose of the Study:
- To evaluate the long-term safety of liothyronine (LT3) therapy compared to levothyroxine (LT4)-only therapy.
- To identify specific safety outcomes associated with LT3 use in a real-world clinical setting.
- To investigate potential risk factors, such as thyroid cancer history and duration of therapy, influencing LT3 safety.
Main Methods:
- A retrospective multicenter study utilizing the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM).
- LT3 users (≥90 days LT3 prescription) were propensity score matched (1:4) with LT4-only users.
- Safety outcomes included osteoporosis, cardiovascular disease (heart failure, stroke), cancer, anxiety, and mood disorders.
Main Results:
- The study identified 1434 LT3 users and 3908 LT4-only users.
- LT3 users exhibited a statistically significant higher incidence rate of heart failure (IRR=1.664) and stroke (IRR=1.757) compared to LT4-only users.
- Subgroup analysis revealed increased heart failure risk in LT3 users with thyroid cancer history and longer LT3 duration (≥52 weeks). Stroke risk was elevated in LT3 users without thyroid cancer history but with longer LT3 duration.
Conclusions:
- Long-term liothyronine (LT3) use is associated with an increased risk of heart failure and stroke.
- The risks appear heightened in patients with a history of thyroid cancer and those on LT3 therapy for over 52 weeks.
- Clinicians should carefully consider these cardiovascular risks when prescribing LT3, particularly for long-term use in thyroid cancer patients.
Abstract:
Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM). We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder. We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002-2.764, p = 0.049) and stroke (IRR = 1.757, CI 1.073-2.877, p = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy. The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations.
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