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DITPA (3,5-Diiodothyropropionic Acid), a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial Veterans Affairs Cooperative Study
Abstract
Background—In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. Methods and Results—This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n=57 to DITPA, n=29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure-specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (−20%), low-density lipoprotein cholesterol (−30%), and body weight (−11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. Conclusions—DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.
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“A small RCT [85] in patients with dilated cardiomyopathy showed beneficial effects of medium-term (3 months) levothyroxine treatment on cardiac performance, whereas another RCT [86] showed that the TH analogue 3,5 di-iodothyropropionic acid improved some hemodynamic variables in heart failure.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [86]
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Metadata
- Authors
- Goldman, S., McCarren, M., Morkin, E., Ladenson, P. W., Edson, R., Warren, S., Ohm, J., Thai, H., Churby, L., Barnhill, J., O'Brien, T., Anand, I., Warner, A., Hattler, B., Dunlap, M., Erikson, J., Shih, M.-C., & Lavori, P.
- Affiliations
- University of Arizona (US)
- From Cardiology, Southern Arizona VA Health Care System (S.G., J.O., H.T.), Tucson, Ariz; VA Pharmacy Benefits Management (M.M.), Hines, Ill; University of Arizona (E.M.), Tucson, Ariz; Johns Hopkins University (P.W.L.), Baltimore, Md; R&D Service (R.E., L.C., M.-C.S., P.L.), Veterans Affairs Medical Center, Palo Alto, Calif; R&D Service (S.W., J.B.), Veterans Affairs Medical Center, Albuquerque, NM; Cardiology (T.O.), Veterans Affairs Medical Center, Charleston, SC; Cardiology (I.A.),...
- ORCID
- Venue
- Circulation
- Published
- 2009-06-23
- Volume
- 119
- Issue
- 24
- Pages
- 3093-3100
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2146450311
- Cited by
- 117
- References
- 28
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 8 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- thyroid hormone analogs, congestive heart failure, cardiac index, systemic vascular resistance, serum cholesterol, TSH suppression, drug tolerability, fatigue, hypothyroidism
- MeSH terms
- Adolescent, Adult, Aged, Body Weight, Cholesterol, Diiodothyronines, Double-Blind Method, Fatigue, Female, Gastrointestinal Diseases, Heart Failure, Humans, Lipoproteins, LDL, Male, Middle Aged, Propionates, Thyroid Hormones, United States, United States Department of Veterans Affairs, Vascular Resistance
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