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Research Article: Effect of levothyroxine on major adverse cardiovascular events in patients with hypothyroidism and cardiovascular disease

Date Published: 2025-08-26

Abstract:
This study aimed to evaluate the effectiveness of levothyroxine, compared to non-levothyroxine treatment, in preventing adverse cardiovascular events and mortality in patients with hypothyroidism and cardiovascular disease (CVD). This is a retrospective study utilizing medical record data from the Yinzhou Regional Health Care Database. The analysis included patients newly diagnosed with hypothyroidism between July 2006 and December 2021 who also had pre-existing CVD at the time when they received the first hypothyroidism diagnosis. The primary outcome measure was the occurrence of three-point major adverse cardiovascular events (3P-MACE), which included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes comprised all-cause mortality, all-cause hospitalization, and cardiovascular-related hospitalization. Propensity score matching was used to match levothyroxine users with non-users on a 1:1 basis. Cox proportional hazard models were employed to compare the risk of outcomes between users and non-users, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. In the matched cohort ( n = 1,332 in each group), 417 patients experienced 3P-MACE. Compared to those not treated with levothyroxine, patients receiving levothyroxine showed a significantly reduced risk of 3P-MACE (HR, 0.67; 95% CI, 0.55–0.82, p < 0.01), all-cause death (HR, 0.24; 95% CI, 0.16–0.35, p < 0.01), all-cause hospitalization (HR, 0.23; 95% CI, 0.21–0.26, p < 0.01), and cardiovascular-related hospitalization (HR, 0.69; 95% CI, 0.59–0.82, p < 0.01). Levothyroxine may improve major cardiovascular outcomes and decrease all-cause hospital admissions in patients with hypothyroidism and CVD.

Introduction:
Hypothyroidism is a prevalent pathological condition characterized by the thyroid gland’s inability to produce adequate thyroid hormones to fulfill the body’s metabolic needs ( 1 ). Hypothyroidism is primarily classified into overt hypothyroidism (OH) and subclinical hypothyroidism (SCH). The prevalence of OH and SCH in the general population ranges from 0.3% and 3.7% in the USA and from 0.2% and 5.3% in Europe, with variations depending on the specific definitions applied ( 2 – 7 ). A large cross-sectional study…

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