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Original Investigation
July 21, 2020

Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction: A Randomized Clinical Trial

Author Affiliations
  • 1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
  • 2Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
  • 3Department of Endocrinology, Gateshead Health NHS Foundation Trust, Gateshead, United Kingdom
  • 4Department of Endocrinology and Cardiology, South Tyneside and Sunderland NHS Foundation Trust, Sunderland, United Kingdom
  • 5Department of Cardiology, Northumbria Healthcare NHS Foundation Trust, Cramlington, United Kingdom
  • 6Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
  • 7Department of Cardiology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom
  • 8Leeds Institute of Clinical Trials Research, University of Leeds, United Kingdom
  • 9Leeds University and Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
JAMA. 2020;324(3):249-258. doi:10.1001/jama.2020.9389
Visual Abstract. Effect of Levothyroxine on LVEF in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction
Effect of Levothyroxine on LVEF in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction
Key Points

Question  Does levothyroxine treatment improve left ventricular function in patients with subclinical hypothyroidism presenting with acute myocardial infarction?

Findings  In this randomized clinical trial that included 95 participants with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks (mean left ventricular ejection fraction, 53.8% vs 56.1%, respectively).

Meaning  These findings do not support treatment of subclinical hypothyroidism in patients with 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 Participants  A 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 Measures  The 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 Relevance  In 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.

Trial Registration  isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169

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