Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial

BACKGROUND: Cardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health. METHODS/DESIGN: ThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes. ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH. Setting: Patients will be recruited from five hospitals in the North East of England. Participants: One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease. Intervention: Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo. Randomisation: Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/− 7) days of AMI. Blinding: Assignment to either the LT4 or placebo arm will be double-blinded. Outcomes: The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology. DISCUSSION: There is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes. TRIAL REGISTRATION: ISRCTN number: ISRCTN52505169. Date of registration: 09/01/2015