Levothyroxine fails to improve LV function in subclinical hypothyroidism, acute MI
Among patients with subclinical hypothyroidism and acute MI, treatment with levothyroxine demonstrated no significant improvement in left ventricular function compared with placebo, researchers reported.
According to research published in JAMA, there was also no difference between the levothyroxine (Eltroxin, Amdipharm) and placebo groups in LV volumes, infarct size, adverse events and patient-reported outcome measures.
“A number of observational studies to date had demonstrated that subclinical hypothyroidism in patients with acute cardiac diseases including acute MI was associated with higher mortality risk,” Salman Razvi, MD, clinical senior lecturer and consultant at the Institute of Genetic Medicine at Newcastle University, U.K., told Healio. “This trial shows that treatment does not seem to confer benefit on LV ejection fraction, a strong prognostic marker in acute MI patients.”
For this double-blind randomized controlled trial, 95 participants with hypothyroidism (mean age, 64 years; 77% men; 69% with STEMI) were enrolled to receive once-daily levothyroxine therapy or placebo for 52 week to determine the effects of thyroid treatment on LV function.
LV function after levothyroxine treatment
Levothyroxine treatment aimed for serum thyrotropin levels between 0.4 mU/L and 2.5 mU/L. LV ejection fraction was assessed using MRI and adjusted for age, sex, acute MI type, affected coronary artery territory and LVEF at baseline. Secondary outcomes included LV volume, infarct size, adverse events in addition to patient-reported outcomes that included health status, health-related quality of life and depression.
Median achieved median thyrotropin level was 5.7 mU/L.
In the levothyroxine therapy group, mean LVEF was 51.3% at baseline and 53.8% at 52 weeks. In the placebo group, mean LVEF was 54% at baseline and 56.1% at 52 weeks (adjusted between-group difference, 0.76%; 95% CI, 0.93 to 2.46; P = .37).
“It is still unclear if treatment of more severe subclinical hypothyroidism (serum thyrotropin > 10 mIU/L) or those with reduced LV function at baseline may still be beneficial,” Razvi said in an interview. “A significant proportion of patients with subclinical hypothyroidism on the first blood test (at the time of admission) had normalized their thyroid function test on repeat testing 7 to 10 days later. This finding suggests that one test alone is unreliable in diagnosing a state of thyroid dysfunction.”
Secondary outcomes of levothyroxine treatment
At week 52, none of the measurements including LV volume per body surface area (66.7 mL/m2 in the levothyroxine group vs. 70.4 mL/m2 in the placebo group), systolic volume per body surface area (31.1 mL/m2 in the levothyroxine group vs. 31.4 mL/m2 in the placebo group) or cardiac output (4.1 L/min in the levothyroxine group vs. 4.6 L/min in the placebo group) differed significantly between the treatment and placebo groups.
Researchers observed no significant differences for infarct size (5.8% in the levothyroxine group vs. 8.4% in the placebo group) or the LV mass (adjusted between-group difference, 1.97 g; 95% CI, 4.43 to 8.37).
Moreover, there were no observable differences in patient-reported outcomes at 52 weeks between participants who received levothyroxine therapy or placebo:
SF-12v2 mean physical component score (adjusted between-group difference, 0.14; 95% CI, 4.54 to 4.23; P = .95);
SF-12v2 mean mental component score (adjusted between-group difference, 3.03; 95% CI, 7.3 to 1.24; P = .16);
median Minnesota Living with Heart Failure Questionnaire score (adjusted between-group difference, 3.74; 95% CI, 10.6 to 3.08; P = .28); and
median Center for Epidemiologic Studies Depression Scale score (adjusted between-group difference, 3.13; 95% CI, 0-6.27; P = .05).
"To any patient who has had a heart attack and has been diagnosed with subclinical hypothyroidism, I would advise that they consult their GP on whether levothyroxine is likely to be of benefit,” Razvi said in a press release. “The results of our trial suggest that all such patients should have their thyroid function rechecked after a few weeks. Treatment with levothyroxine should not be started routinely in such patients. Furthermore, international guidelines should be amended to reflect this finding."
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