Assessing the Cardiovascular Effects of Levothyroxine Use in an Ageing UK Population with Subclinical Hypothyroidism: Emulated Target Trial (ACEL-UK-ETT)
Main finding · Cardiovascular eventsResult — go to the resultAdjusted hazard ratio 0.82 CI 0.74–0.91Authors' conclusion
Long-term levothyroxine use in older adults with SCH was associated with lower long-term cardiovascular and all-cause mortality risks, with no significant harm to bone health. Age-specific thyrotropin levels should guide treatment decisions.
Study context
- Population
- Adults over 50 years with subclinical hypothyroidism (SCH) (TSH 4.1–10.0mU/L, FT4 10.0–24.0 pmol/L), The Health Improvement Network, 2006–2022; median age 66 [59–75] years, 76.7% female62% received LT4
- Participants
- 22,621 participants
- Exposure
- LT4 vs no LT4 in older adults with SCH
- Outcome
- Cardiovascular events:
- Angina
- MI
- Peripheral vascular disease
- Stent procedures
- Stroke
- Follow-up
- 10 years
Methodological detailsobservational cohort study, inverse probability of treatment weighting, 10-year outcomes
- Observational cohort study
- Inverse probability of treatment weighting
- 10-year outcomes
Main finding
Cardiovascular events
Adjusted hazard ratio
0.82
CI 0.74–0.91
P < 0.0001
Levothyroxinevs No levothyroxine
aHR 0.82 (CI 0.74–0.91); P < 0.0001
As reported in the abstract
Observational data: associations, not effects.
Secondary outcomes
| Outcome | aHR (CI) | P value | |
|---|---|---|---|
| All-cause mortalityIPTW-adjusted | 0.71 (0.67–0.75) | P < 0.0001 | |
| 0.512Adjusted hazard ratio (log scale) |
Cardiovascular events by age-specific TSH and treatment duration
- Cardiovascular benefits limited to patients with TSH above the age-specific range and after at least five years of treatment
Safety
| Outcome | aHR (CI) | P value | |
|---|---|---|---|
| Bone events (fragility fractures or osteoporosis)IPTW-adjusted | 1.04 (0.93–1.17) | P = 0.45 | |
| 0.512Adjusted hazard ratio (log scale) |
Original publication
Assessing the Cardiovascular Effects of Levothyroxine Use in an Ageing UK Population with Subclinical Hypothyroidism: Emulated Target Trial (ACEL-UK-ETT). Thyroid. Published 19 February 2026. doi:10.
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