Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline

Abstract

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 (PϽ0.005) and an increase in systolic blood pressure (PϽ0.05) and left ventricular radionuclide ejection fraction (PϽ0.05) 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.

Effects of pentoxifylline on inflammatory markers and blood pressure

“…In patients with ischemic cardiomyopathy, adding pentoxifylline to standard therapy (which included beta blockers) was associated with reduction in plasma concentration of inflammatory markers TNF-alpha and CRP, marker of apoptosis (Fas/Apo-1) and correlated with improvement of left ventricular ejection fraction [32].…”

“…After assessment, 15 RCTs achieved the inclusion criteria and were used for the final meta-analysis [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and these reported 18 treatment arms. A total of 739 individuals participated in the selected trials and 377 of them were allocated to the pentoxifylline group and 362 subjects to control group.…”

Inflammatory Biomarkers in Heart Failure

“…Pentoxifylline, an agent known to inhibit TNF-α production, among other physiologic effects, has similarly shown favorable effects of HF symptoms and ejection fraction in preliminary studies. 34,35 These promising data will require confirmation in larger studies.…”

Pentoxifylline in Heart Failure: A Meta‐Analysis of Clinical Trials

“…The first six studies [5][6][7][8][9][10] are from a single center with a meta-analysis already performed for the five randomized studies [11]. One of these studies was excluded because of its before/after design [8].…”