TY - JOUR

T1 - Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism

T2 - Pooled Individual Results of Two Randomised Controlled Trials

AU - Zijlstra, Laurien E.

AU - Jukema, J. Wouter

AU - Westendorp, Rudi G. J.

AU - Du Puy, Robert S.

AU - Poortvliet, Rosalinde K. E.

AU - Kearney, Patricia M.

AU - O'Keeffe, Linda

AU - Dekkers, Olaf M.

AU - Blum, Manuel R.

AU - Rodondi, Nicolas

AU - Collet, Tinh-Hai

AU - Quinn, Terence J.

AU - Sattar, Naveed

AU - Stott, David J.

AU - Trompet, Stella

AU - den Elzen, Wendy P. J.

AU - Gussekloo, Jacobijn

AU - Mooijaart, Simon P.

PY - 2021

Y1 - 2021

N2 - BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged >= 65 years for TRUST (n=737) and >= 80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7-81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38 +/- SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 +/- 3.3 mIU/L in the placebo group, compared with 3.66 +/- 2.1 mIU/L in the levothyroxine group (pConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.

AB - BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged >= 65 years for TRUST (n=737) and >= 80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7-81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38 +/- SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 +/- 3.3 mIU/L in the placebo group, compared with 3.66 +/- 2.1 mIU/L in the levothyroxine group (pConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.

KW - cardiovascular disease

KW - levothyroxine

KW - randomised controlled trial

KW - subclinical hypothyroidism

KW - older adults

KW - ADULTS

KW - ASSOCIATION

KW - PROTOCOL

U2 - 10.3389/fendo.2021.674841

DO - 10.3389/fendo.2021.674841

M3 - Journal article

C2 - 34093444

VL - 12

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

M1 - 674841

ER -