Levothyroxine Treatment of Subclinical Hypothyroidism and the Risk of Adverse Cardiovascular Events.

Levothyroxine treatment of subclinical hypothyroidism was associated with a small decreased risk of MACE compared to no treatment.

• Hazard ratio for MACE was 0.88 (95% CI: 0.83-0.93) for levothyroxine-treated versus untreated individuals.
• Incidence rate for MACE among levothyroxine-treated individuals was 12.8 per 1000 person-years (CI: 12.2-13.3).
• Incidence rate for MACE among untreated individuals was 13.9 per 1000 person-years (CI: 13.4-14.3).
• MACE was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality.

The study cohort consisted of 153,892 matched individuals with subclinical hypothyroidism, with a mean age of 62.8 years and predominantly female composition.

• 76,946 levothyroxine-treated individuals were matched to 76,946 untreated individuals.
• Mean age of the study cohort was 62.8 years.
• 76.5% of the cohort were women.
• Matching was based on age, sex, calendar time, duration of SCH, and time-conditional propensity score.

The study used a prevalent new-user design with a population-based cohort from the United Kingdom Clinical Practice Research Datalink.

• The base cohort included individuals aged ≥18 years with incident SCH identified between 1998 and 2018.
• Subclinical hypothyroidism was defined as having at least two TSH levels between 5 and 10 mU/L within one year.
• The prevalent new-user design was employed to compare levothyroxine treatment versus no treatment.

The median follow-up time for the study cohort was relatively short at 1.6 years.

• Median follow-up time was 1.6 years with an interquartile range of 0.5-4.2 years.
• The relatively short follow-up may limit the ability to detect long-term cardiovascular effects of levothyroxine treatment.

The authors caution that residual confounding should be considered when interpreting the association between levothyroxine treatment and reduced cardiovascular risk.

• The observational nature of the study limits causal inference.
• Despite propensity score matching, unmeasured or residual confounders may have influenced the results.
• The authors note uncertainty as to whether treatment of subclinical hypothyroidism is truly associated with improved cardiovascular outcomes.