Table 1.

Summary table of the use of levothyroxine in SCH to reduce CVD risks.

Authors	Year of Publication	Sample Size	Study Design	Population	Results
Razvi et al. (21)	2010	91	Cohort study	Middle-aged community-dwelling adults with SCH enrolled in the Whickham Study, a population-based cross-sectional study in northern England with 20 years of follow up.	Reduced all-cause mortality in those treated with levothyroxine: HR 0.22, 95% CI 0.06–0.81 (p = 0.02).
Razvi et al. (52)	2012	4,735	Cohort study	3,093 individuals age 40–70 years and 1,642 individuals age 71–107 years old with SCH from the United Kingdom General Practitioner Research Database. The median levothyroxine dose was 75 mcg daily.	In younger individuals (age 40–70 years) who received treatment with levothyroxine, there were fewer ischemic heart disease events (HR 0.61, 95% CI 0.39–0.95), deaths due to circulatory diseases (HR 0.54, 95% CI 0.37–0.92), and deaths due to any cause (HR 0.36, 95% CI 0.19–0.66).
Andersen MN et al. (53)	2015	12,212	Cohort study	Primary care adult patients 18 years or older in Copenhagen, Denmark diagnosed with SCH between 2000 and 2009	No association between treatment with levothyroxine and myocardial infarction, CVD death, or all-cause mortality. Benefit of levothyroxine treatment for all-cause mortality in patients less than 65 years old (incidence rate ratio 0.63, 95% CI 0.40–0.99).
Anderson MN et al. (54)	2016	1,192	Cohort study	Adult clinic patients 18 years or older in Denmark with existing heart disease diagnosed with SCH from 1997 to 2011.	No association between treatment with levothyroxine and major adverse cardiac events, all-cause mortality, MACE, or hospital admissions.
Stott et al. (55)	2017	737	Randomized controlled trial	Adults 65 years or older from Scotland, Ireland, the Netherlands, and Switzerland with untreated SCH randomized to a median daily levothyroxine dose of 50 mcg or placebo.	No significant differences in fatal or nonfatal cardiovascular events (HR 0.89, 95% CI 0.47–1.69), new-onset atrial fibrillation (HR 0.80, 95% CI 0.35–1.80), or all-cause mortality (HR 1.91, 95% 0.65–5.60) between the levothyroxine and placebo groups.
Blum et al. (56)	2018	158	Randomized controlled trial	Subset of participants from the Stott et al. study: Adults 65 years or older from Scotland, Ireland, the Netherlands, and Switzerland with untreated SCH randomized to a median daily levothyroxine dose of 50 mcg or placebo.	No significant differences in mean carotid intima media thickness (p = 0.30), maximum carotid intima media thickness (p = 0.35), or maximum plaque thickness (p = 0.86) between the levothyroxine and placebo groups.

SCH, subclinical hypothyroidism; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval; MACE, major adverse cardiovascular events.