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

There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. We conducted a population-based cohort study using a prevalent new-user design. The study utilized data from the United Kingdom Clinical Practice Research Datalink. We identified a base cohort of individuals aged ≥18 years with incident SCH defined as having at least two TSH levels between 5 and 10 mU/L within one year between 1998 and 2018. We matched 76,946 levothyroxine treated to 76,946 untreated individuals based on age, sex, calendar time, duration of SCH, and time-conditional propensity score. We compared individuals with SCH treated with levothyroxine with individuals with no treatment. Levothyroxine treatment versus no treatment. The primary outcome, MACE, was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality. The mean age of the study cohort was 62.8 years, and 76.5% were women. During a median follow-up time of 1.6 years (interquartile range: 0.5-4.2), the incidence rate for MACE among individuals treated with levothyroxine was 12.8 per 1000 person-years; confidence interval (CI): 12.2-13.3 and 13.9 per 1000 person-years; CI: 13.4-14.3 among nontreated individuals. Levothyroxine treatment was associated with a small decreased risk of MACE (hazard ratio: 0.88; CI: 0.83-0.93). Levothyroxine treatment of SCH was associated with a small decreased risk of MACE. However, given the observational nature of the study, residual confounding should be considered in the interpretation of this finding.