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Effect of levothyroxine on left ventricular ejection fraction in patients with subclinical hypothyroidism and acute myocardial infarction: a randomized clinical trial

Lookup NU author(s): Dr Avais Jabbar, Lorna Ingoe, Dr Shahid Junejo, Dr Peter Carey, Dr Honey Thomas, Dr Jehill Parikh, Dr David Austin, Dr Kieren Hollingsworth, Dr Deborah Stocken, Professor Simon PearceORCiD, Professor Azfar Zaman, Dr Salman Razvi



This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Medical Association, 2020.

For re-use rights please refer to the publisher's terms and conditions.


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 six 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 mcg 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 (standard deviation) age was 63.5 (9.5) years, 72 (76.6%) were males, 65 (69.1%) had ST-segment elevation myocardial infarction, the median (interquartile range) serum thyrotropin was 5.7 mU/L (4.8 – 7.3 mU/L) and mean free thyroxine was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 (89.5%) patients. The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8% in the levothyroxine group compared to 54.0% and 56.1% in the placebo group; adjusted difference in groups (95% confidence interval) of 0.76% (-0.93% to 2.46%), p=0.37. None of the six 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 to 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. ISRCTN Number: 52505169

Publication metadata

Author(s): Jabbar A, Ingoe L, Junejo S, Carey P, Addison C, Thomas H, Parikh JD, Austin D, Hollingsworth KG, Stocken DD, Pearce SHS, Greenwood JP, Zaman A, Razvi S

Publication type: Article

Publication status: Published

Journal: JAMA: The Journal of the American Medical Association

Year: 2020

Volume: 324

Issue: 3

Pages: 249-258

Print publication date: 21/07/2020

Online publication date: 21/07/2020

Acceptance date: 15/05/2020

Date deposited: 30/05/2020

ISSN (print): 0098-7484

ISSN (electronic): 1538-3598

Publisher: American Medical Association


DOI: 10.1001/jama.2020.9389


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