Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction

Abstract

IMPORTANCE Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis.OBJECTIVE To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. DESIGN, SETTING, AND PARTICIPANTSA double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017.INTERVENTIONS Levothyroxine treatment (n = 46) commencing at 25 μg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. RESULTS Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, −0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. CONCLUSIONS AND RELEVANCEIn this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction.

Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease

“…Multiple studies have suggested improvement in cholesterol parameters, blood pressure, and various markers of cardiac and vascular structure/function with levothyroxine treatment in SCH (25,(57)(58)(59)(60)(61), but generally these studies were small, the results need to be replicated, and any improvement in CVD risk factors with levothyroxine treatment may not ultimately translate into a reduction in CVD risk. A recent double-blind, randomized controlled trial that enrolled patients with acute myocardial infarction and SCH in hospitals in the United Kingdom found no difference in the primary outcome of left ventricular ejection fraction at 52 weeks, comparing the 46 participants in the treatment group (levothyroxine 25 mcg daily titrated to serum TSH levels between 0.4-2.5) with the 49 participants in the placebo group (62). An older small study of 40 women with mild SCH randomized participants to 50 mcg of levothyroxine daily or placebo: after 6 months, there was no significant difference in cholesterol, triglycerides, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, or other parameters studied (63).…”

An Underdiagnosed Hypothyroidism and Its Clinical Significance in Patients with Advanced Hepatocellular Carcinoma

“…Although levothyroxine supplementation is easy and convenient for patients with overt hypothyroidism, guidelines do not recommend routine levothyroxine supplementation in asymptomatic patients with subclinical hypothyroidism [26,27]. A recent study on patients with subclinical hypothyroidism and acute myocardial infarction failed to demonstrate the benefit of levothyroxine supplement in improving the left ventricular ejection function [28]. Thus, levothyroxine should not be routinely given to patients with advanced HCC and subclinical hypothyroidism unless future studies prove otherwise.…”

Best Achievements in Clinical Thyroidology in 2020

“…www.e-enm.org 31 two preliminary but important results were reported from double-blind, randomized controlled trials of LT4 replacement in subjects with subclinical hypothyroidism. Jabbar et al [2] investigated the effects of LT4 in patients with subclinical hypothyroidism presenting with acute myocardial infarction, but failed to show any benefits for outcomes such as left ventricular function, adverse events, and quality of life after 52 weeks of LT4 treatment. Furthermore, de Montmollin et al [3] reported that LT4 replacement failed to improve hypothyroid symptoms or tiredness scores at 1 year in subjects aged ≥65 years with subclinical hypothyroidism (4.6≤ TSH ≤11.9 mU/L) in a secondary analysis of the randomized, placebo-controlled Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial (TRUST).…”