Long-term outcome in levothyroxine treated patients with subclinical hypothyroidism and concomitant heart disease

CONTEXT: Subclinical hypothyroidism is a common condition that may lead to impaired cardiac function.

OBJECTIVE: To examine the effects of levothyroxine treatment in patients with subclinical hypothyroidism and heart disease.

DESIGN: Register-based historical cohort study.

SETTING AND PARTICIPANTS: Danish primary care patients and hospital outpatients aged 18 years and older with established heart disease who were diagnosed with subclinical hypothyroidism in 1997 - 2011. Patients were stratified according to whether or not they claimed a subsequent prescription of levothyroxine. Event rates and incidence rate ratios (IRR) were calculated by use of time-dependent multi-variable Poisson regression models.

MAIN OUTCOME MEASURES: All-cause mortality, MACE (major adverse cardiac events) defined as cardiovascular death, fatal or non-fatal MI and stroke, and all-cause hospital admissions.

RESULTS: Of 61,611 patients with a diagnosis of cardiac disease having their first time thyroid function testing, 1,192 patients with subclinical hypothyroidism (mean age 73.6 [SD ± 13.3] years, 63.8% female) were included, of whom 136 (11.4%) were treated with levothyroxine. During a median follow-up time of 5.6 years (IQR 6.5), 694 (58.2%) patients died. Patients treated with levothyroxine displayed no significantly increased risk of all-cause mortality (adjusted IRR 1.17 [95% CI: 0.90-1.52]), MACE (adjusted IRR 1.08 [95% CI: 0.80-1.45]), or hospital admission (adjusted IRR 0.94 [95% CI: 0.71-1.24]), when compared to patients not treated with levothyroxine.

CONCLUSION: Levothyroxine treatment in patients with subclinical hypothyroidism and heart disease was not associated with a significant benefit nor risk of all-cause mortality, MACE or hospital admission in this large real-world cohort study.