Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine: An Observational Nationwide Cohort Study

Mette Nygaard Einfeldt; Anne-Marie Schjerning Olsen; Søren Lund Kristensen; Usman Khalid; Jens Faber; Christian Torp-Pedersen; Gunnar H Gislason; Christian Selmer

doi:10.1210/jc.2018-01604

Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine: An Observational Nationwide Cohort Study

Mette Nygaard Einfeldt, Anne-Marie Schjerning Olsen, Søren Lund Kristensen, Usman Khalid, Jens Faber, Christian Torp-Pedersen, Gunnar H Gislason, Christian Selmer

Department of Clinical Medicine

4 Citations (Scopus)

Abstract

CONTEXT: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF).

OBJECTIVE: Examining the effects of L-T4 in patients with HF.

DESIGN: Retrospective cohort study.

SETTING AND PARTICIPANTS: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models.

MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs).

RESULTS: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment.

CONCLUSION: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	104
Issue number	5
Pages (from-to)	1725-1734
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2018-01604
Publication status	Published - 2019

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Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine: An Observational Nationwide Cohort Study. / Einfeldt, Mette Nygaard; Olsen, Anne-Marie Schjerning; Kristensen, Søren Lund et al.
In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 5, 2019, p. 1725-1734.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{0b3f70992303409598b2dd9cdd72304b,

title = "Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine: An Observational Nationwide Cohort Study",

abstract = "CONTEXT: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF).OBJECTIVE: Examining the effects of L-T4 in patients with HF.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models.MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs).RESULTS: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment.CONCLUSION: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment.",

author = "Einfeldt, {Mette Nygaard} and Olsen, {Anne-Marie Schjerning} and Kristensen, {S{\o}ren Lund} and Usman Khalid and Jens Faber and Christian Torp-Pedersen and Gislason, {Gunnar H} and Christian Selmer",

note = "Copyright {\textcopyright} 2019 Endocrine Society.",

year = "2019",

doi = "10.1210/jc.2018-01604",

language = "English",

volume = "104",

pages = "1725--1734",

journal = "The Journal of clinical endocrinology and metabolism",

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T1 - Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine

T2 - An Observational Nationwide Cohort Study

AU - Einfeldt, Mette Nygaard

AU - Olsen, Anne-Marie Schjerning

AU - Kristensen, Søren Lund

AU - Khalid, Usman

AU - Faber, Jens

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - Selmer, Christian

PY - 2019

Y1 - 2019

N2 - CONTEXT: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF).OBJECTIVE: Examining the effects of L-T4 in patients with HF.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models.MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs).RESULTS: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment.CONCLUSION: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment.

AB - CONTEXT: Hypothyroidism has detrimental effects on the cardiovascular system, but controversy remains concerning the benefits of levothyroxine (L-T4) substitution in patients with heart failure (HF).OBJECTIVE: Examining the effects of L-T4 in patients with HF.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: All Danish citizens aged ≥18 years diagnosed with HF between 1997 and 2012. L-T4 treatment was identified from nationwide registers. Incidence rate ratios (IRRs) were calculated with Poisson regression models.MAIN OUTCOME MEASURES: All-cause mortality, myocardial infarction (MI), cardiovascular death, and major adverse cardiovascular events (MACEs).RESULTS: A total of 224,670 patients were diagnosed with HF [mean age 70.7 (SD ± 14.7) years, 53% male]. Of these, 6560 patients were treated with L-T4 at baseline, and 9007 patients initiated L-T4 during follow-up. A total of 209,103 patients did not receive L-T4. During a median follow-up of 4.8 years [interquartile range (IQR) 9.2] 147,253 patients died. Increased risk of all-cause mortality (IRR 1.25; 95% CI, 1.21 to 1.29; IRR 1.13; 95% CI, 1.10 to 1.16), cardiovascular death (IRR 1.23; 95% CI, 1.18 to 1.27; IRR 1.11; 95% CI, 1.08 to 1.15), and MACE (IRR 1.26; 95% CI, 1.22 to 1.31; IRR 1.05; 95% CI, 1.02 to 1.09) was observed for treatment ongoing at baseline and initiated during follow-up, respectively. Increased risk of MI (IRR 1.32; 95% CI, 1.23 to 1.41) was observed for ongoing treatment, and reduced risk (IRR 0.87; 95% CI, 0.81 to 0.93) was observed for incident treatment.CONCLUSION: Ongoing and incident L-T4 treatment in patients with HF was associated with an increased risk of all-cause mortality, cardiovascular death, and MACE. Increased risk of MI was observed for ongoing treatment, and reduced risk was observed for incident treatment.

U2 - 10.1210/jc.2018-01604

DO - 10.1210/jc.2018-01604

M3 - Journal article

C2 - 30517746

SN - 0021-972X

VL - 104

SP - 1725

EP - 1734

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 5

ER -

Long-Term Outcome in Patients With Heart Failure Treated With Levothyroxine: An Observational Nationwide Cohort Study

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