From the Journals

Levothyroxine: No LV benefit in subclinical hypothyroidism with MI


For patients with acute myocardial infarction (MI) and mild subclinical hypothyroidism (SCH), treatment with levothyroxine does not improve left ventricular function, according to results of the Thyroid in Acute Myocardial Infarction (ThyrAMI-2) trial.

“SCH is common, affecting approximately 10% of the adult population, and has been associated with worse outcomes in patients with cardiovascular disease in observational studies,” Salman Razvi, MD, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, England, said in an interview.

This study shows that levothyroxine treatment for patients with SCH and acute MI is “unlikely to be of benefit,” he said.

“This study says that treating the thyroid failure does not help nor harm such patients,” Terry F. Davies, MD, director, division of endocrinology, diabetes, and bone diseases, Mount Sinai Beth Israel Medical Center, New York, said in an interview. He was not involved in the study, which was published online July 21 in JAMA.

Participants included 95 adults (mean age, 63.5 years; 72 men) with persistent mild SCH who presented with acute MI at six hospitals in the United Kingdom. Most (69%) had ST-segment elevation MI.

Inclusion criteria were age older than 18 years and serum thyrotropin level >4.0 mU/L with a normal free thyroxine level on two occasions 7-10 days apart and with one thyrotropin value <10 mU/L.

Forty-six participants were randomly allocated to receive levothyroxine starting at 25 mcg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L and 49 to matching placebo capsules taken once daily for 52 weeks.

The primary outcome was left ventricular ejection fraction (LVEF) at 52 weeks, assessed via MRI, with adjustment for age, sex, acute MI type, affected coronary artery territory, and baseline LVEF.

Secondary outcomes were LV volume, infarct size, adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression.

The median daily dose of levothyroxine at the end of the study was 50 mcg. Adherence to study medication was 94% during the course of the study.

At week 52, mean LVEF improved from 51.3% at baseline to 53.8% in the levothyroxine group and from 54.0% to 56.1% in the placebo group.

The difference was not significant between groups, with an adjusted between-group difference of 0.76% (95% confidence interval, –0.93% to 2.46%; P = .37).

There were also no significant differences in any of the secondary outcomes. There were 15 (33.3%) cardiovascular adverse events in the levothyroxine group and 18 (36.7%) in the placebo group.

Recent clinical practice guidelines have highlighted a lack of high-quality data to make recommendations regarding the management of mild SCH, particularly for patients with cardiovascular disease, Dr. Razvi and colleagues noted in their article.

“On the basis of these findings, screening for and subsequent treatment of subclinical hypothyroidism in patients with acute myocardial infarction to preserve LV function is not justified,” they concluded.

Important caveats

The investigators noted several important caveats and limitations. The trial recruited patients with mild SCH because this group constitutes the majority of patients with SCH and for whom there is the “greatest uncertainty” regarding treatment efficacy. It’s not known whether targeting treatment for individuals with more severe disease may be beneficial.

The therapeutic benefit of levothyroxine may have been blunted, owing to the delay between coronary occlusion and the start of levothyroxine (median delay, 17 days). It’s unclear whether earlier treatment or treatment for a longer period may be beneficial.

But Dr. Davies noted that “treatment is usually avoided in the emergency situation,” and therefore he doesn’t think the treatment delay is a limitation; rather, “it would appear prudent,” he said in the interview.

“The real issues with an otherwise very careful study is the small size of the population despite the statistical assessment that this was all that was needed and, secondly, the small dose of thyroxine used,” Dr. Davies said.

The authors agree that the low dose of levothyroxine is a limitation. The median dose at the end of the study – 50 mcg daily – is “lower than that used in other trials that have demonstrated a benefit of treatment on endothelial function and lipid profiles,” they pointed out.

Dr. Davies noted that thyroid tests are “usually routine” for patients with MI. “Mild subclinical thyroid failure has been associated with worse cardiac outcomes, [but] treating such patients with thyroid hormone is very controversial since thyroid hormone can induce arrhythmias,” he said.

The study was supported in part by the National Institute for Health Research (NIHR) at the University of Leeds. Dr. Razvi received grants from the NIHR and nonfinancial support from Amdipharm Pharmaceuticals UK during the conduct of the study and personal fees from Merck and Abbott Pharmaceuticals outside the submitted work. Dr. Davies has disclosed no relevant financial relationships.

A version of this article originally appeared on

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