CONTEXT: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF).

OBJECTIVE: Examining the effects of L-T4 in patients with HF.

DESIGN: Retrospective cohort study.

SETTING AND PARTICIPANTS: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models.

MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs).

RESULTS: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment.

CONCLUSION: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment.