Long-term Outcome in Heart Failure Patients Treated with Levothyroxine: An Observational Nationwide Cohort Study

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 (IRR) were calculated using Poisson-regression models.

Main Outcome Measures: All-cause mortality, myocardial infarction (MI), cardiovascular death and major adverse cardiovascular events (MACE).

Results: 224,670 patients were diagnosed with HF (mean age 70.7 [SD±14.7] years, 53% male). 6,560 patients were treated with L-T4 at baseline, 9,007 patients initiated L-T4 during follow-up. 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years (IQR 9.2) 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25 [95% CI: 1.21-1.29]) (IRR 1.13 [95% CI: 1.10-1.16]), cardiovascular death (IRR 1.23 [95% CI: 1.18-1.27]) (IRR 1.11 [95% CI: 1.08-1.15]), and MACE (IRR 1.26 [95% CI: 1.22-1.31]) (IRR 1.05 [95% CI: 1.02-1.09]), was observed for treatment on-going at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32 [95% CI: 1.23-1.41]) was observed for on-going treatment, reduced risk (IRR 0.87 [95% CI: 0.81-0.93]) was observed for incident treatment.

Conclusion: On-going 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 on-going treatment, reduced risk was observed for incident treatment.