Published Online
on June 8, 2009

A more recent version of this article appeared on June 23, 2009

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Submitted on November 14, 2008
Accepted on April 10, 2009

DITPA (3,5-Diiodothyropropionic Acid), a Thyroid Hormone Analog to Treat Heart Failure. Phase II Trial Veterans Affairs Cooperative Study

Steven Goldman MD^*, Madeline McCarren PhD, MPH, Eugene Morkin MD, Paul W. Ladenson MD, Robert Edson MA, Stuart Warren JD, PharmD, Janet Ohm MSN, RN, Hoang Thai MD, Lori Churby BA, Jamie Barnhill PhD, Terrence O'Brien MD, Inder Anand MD, Alberta Warner MD, Brack Hattler MD, Mark Dunlap MD, John Erikson MD, Mei-Chiung Shih PhD, and Phil Lavori PhD

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.), Veterans Affairs Medical Center, Minneapolis, Minn; Cardiology (A.W.), Veterans Affairs Medical Center, West Los Angeles, Calif; Cardiology (B.H.), Veterans Affairs Medical Center, Denver, Colo; Cardiology (M.D.), Veterans Affairs Medical Center, Cleveland, Ohio; and Cardiology (J.E.), Veterans Affairs Medical Center, San Antonio, Tex.

^* To whom correspondence should be addressed. E-mail: steven.goldman{at}va.gov.

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.

Key words: cardiac output • hemodynamics • thyroid • heart failure • pharmacology

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