Thyroxine in Acute Myocardial Infarction (ThyrAMI)

Abstract

Importance: Thyroid hormones play a key role in modulating myocardial contractility and vascular function. Subclinical hypothyroidism is associated with worse cardiovascular outcomes, in those without cardiovascular disease, and a poor prognosis in patients with acute myocardial infarction. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function, markers of vascular function and patient reported outcomes in patients with acute myocardial infarction and subclinical hypothyroidism. Hypotheses: Levothyroxine treatment will improve left ventricular function as a primary outcome measure. Furthermore, levothyroxine treatment will decrease thrombus burden, improve clot kinetics, platelet reactivity and endothelial function as well as patient reported outcomes. Design, Setting, and Participants: A double blind, randomized clinical trial conducted in six hospitals in the United Kingdom. Patients with acute myocardial infarction including STsegment 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 outcomes were surrogate markers of vascular function and patient reported outcome measures of health status, health-related quality of life, and depression. ii Results: Among the 95 participants randomized, 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. Levothyroxine treatment did not significantly decrease thrombus burden, improve clot kinetics, decrease platelet reactivity or improve endothelial function. Furthermore, patient reported outcomes were not significantly different between both groups at the study end. 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 low dose levothyroxine, compared to placebo, did not significantly improve left ventricular ejection fraction, markers of vascular function and patient reported outcomes after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction.