The impact of Levothyroxine on cardiac function in older adults with Mild subclinical hypothyroidism: a randomized clinical trial

Gencer, B. et al. (2020) The impact of Levothyroxine on cardiac function in older adults with Mild subclinical hypothyroidism: a randomized clinical trial. American Journal of Medicine, 133(7), 848-856.e5. (doi: 10.1016/j.amjmed.2020.01.018) (PMID:32171774)

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Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function. In a randomized, double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants aged ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone, TSH, 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization, or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function, and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e' ratio) for diastolic function. Secondary outcomes included e' lateral/septal, left atrial volume index and systolic pulmonary artery pressure. 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n=96), while it remained elevated at 5.29 mIU/L with placebo (n=89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs. 62.5%, difference=0.4%, 95%CI -1.8% to 2.5%, P=0.72) and the E/e' ratio (10.6 vs. 10.1, difference 0.4, 95%CI -0.7-1.4, P=0.47). No differences were found for the secondary diastolic function parameters, nor for interaction according to sex, baseline TSH, preexisting heart failure and treatment duration (P-value >0.05). Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism.

Item Type:Articles
Additional Information:This study was supported grants of the Swiss National Science Foundation to NR (SNSF 320030-150025 and 320030-172676), and investigator-driven grants of the Velux Stiftung (974a, to NR) and of the Swiss Heart Foundation (to NR). The TRUST Trial was supported by a research grant (grant agreement number 278148) from the European Union FP7-HEALTH-2011 program).
Keywords:Clinical trials, heart failure, levothyroxine, subclinical hypothyroidism, thyroid.
Glasgow Author(s) Enlighten ID:Stott J, Professor David
Authors: Gencer, B., Moutzouri, E., Blum, M. R., Feller, M., Collet, T.-H., Delgiovane, C., da Costa, B. R., Buffle, E., Monney, P., Gabus, V., Müller, H., Sykiotis, G. P., Kearney, P., Gussekloo, J., Westendorp, R., Stott, D. J., Bauer, D. C., and Rodondi, N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:American Journal of Medicine
ISSN (Online):1555-7162
Published Online:12 March 2020
Copyright Holders:Copyright © 2020 Elsevier Inc.
First Published:First published in American Journal of Medicine 133(7): 846-856.e5
Publisher Policy:Reproduced under a Creative Commons License

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