Levothyroxine Associated With Increased Mortality in Heart Failure
Treatment with levothyroxine in patients with heart failure has not been studied adequately, and controversy about treatment substitution has developed as a result.
Treatment with levothyroxine in patients with heart failure is associated with a higher risk for all-cause mortality, cardiovascular death, and major adverse cardiac events, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
A condition involving low levels of serum triiodothyronine (T3), known as “low T3 syndrome,” is fairly common in patients with heart failure and indicates that less active hormone is available to the heart through blood plasma. When hypothyroidism is treated with levothyroxine, there is often a relatively high thyroxine/T3 ratio in serum with relatively low liothyronine levels in blood, which could further exacerbate the T3-deficient state in patients with chronic heart failure. To examine the effects of levothyroxine in patients with heart failure, researchers conducted a retrospective cohort study that included 224,670 patients hospitalized for heart failure between 1997 and 2012. Of this group, 6560 patients were treated with levothyroxine at baseline, 9007 had levothyroxine initiated during the study period, and the remaining patients did not receive levothyroxine.
At a median follow-up of 4.8 years, 147,253 patients had died. For all-cause mortality, the adjusted incidence rate ratio (IRR) indicated that levothyroxine treatment at baseline was associated with a 25% (95% CI, 1.21-1.29) increased risk for death. Levothyroxine therapy initiated during follow-up was associated with a 13% (95% CI, 1.10-1.16) increased risk for death. For cardiovascular-related death, the adjusted IRR showed that levothyroxine treatment at baseline was associated with a 23% (95% CI, 1.18-1.27) increased risk and initiation during follow-up was associated with an 11% (95% CI, 1.08-1.15) increased risk. There was also an increased risk for myocardial infarction (IRR 1.32; 95% CI, 1.23-1.41) and major adverse cardiac events (IRR, 1.26; 95% CI, 1.22-1.31) with levothyroxine treatment at baseline, but a reduced risk for myocardial infarction (IRR, 0.87; 95% CI, 0.81-0.93) with incident treatment.
The researchers concluded that their findings “do not support the hypothesis that patients with known [heart failure] benefit from levothyroxine substitution. One explanation for this could be that patients who are substituted with levothyroxine do not tolerate thyroid hormone replacement therapy either due to the unclassified severity of their underlying [heart failure] condition or due to potential overtreatment… A randomized controlled trial study is warranted to evaluate the prognostic impact of thyroid dysfunction and thyroid hormone substitution in patients with [heart failure].”
Einfeldt MN, Olsen AS, Kristensen SL, et al. Long-term outcome in heart failure patients treated with levothyroxine: an observational nationwide cohort study [published online December 4, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01604