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(Circulation. 2004;109:750-755.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline

Results of a Randomized Study

Karen Sliwa, MD, PhD; Angela Woodiwiss, PhD; Veuvette N. Kone; Geoffrey Candy, PhD; Danelle Badenhorst; Gavin Norton, MD, PhD; Chris Zambakides, MD; Ferande Peters, MD; Rafique Essop, MD

From the Department of Cardiology (K.S., G.C., C.Z., F.P., R.E.) and Department of Chemical Pathology (V.N.K.), Chris-Hani-Baragwanath Hospital and School of Physiology (A.W., D.B., G.N.), University of the Witwatersrand, Johannesburg, South Africa.

Correspondence to Prof Karen Sliwa, MD, PhD, Department of Cardiology, Chris-Hani Baragwanath Hospital, PO Box 2013, Johannesburg, South Africa, Old Potchroad 100, Soweto. E-mail Hahnle{at}netactive.co.za

Received July 18, 2003; revision received October 23, 2003; accepted October 24, 2003.

Background— Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor- (TNF-), and the marker of apoptosis, Fas/Apo-1.

Methods and Results— In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class (P<0.005) and an increase in systolic blood pressure (P<0.05) and left ventricular radionuclide ejection fraction (P<0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group.

Conclusions— In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.

Key Words: heart failure • cardiomyopathy • pentoxifylline • natriuretic peptides • C-reactive protein

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