Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms.
BACKGROUND
Tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are significantly elevated in patients with congestive heart failure (CHF). Pentoxifylline, a xanthin-derived agent, is known to inhibit the production of TNF-alpha and IL-6. Recent studies have shown that pentoxifylline produces an increase in ejection fraction, a decrease in left-ventricular chamber size and an improvement in clinical status in patients with idiopathic-dilated cardiomyopathy. Therefore, we studied the effects of pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy.


METHODS
Primary endpoint was left-ventricular ejection fraction (LVEF) assessed by contrast 2D echocardiography. Secondary endpoints were concentrations of TNF-alpha, IL-6, brain natriuretic peptide, maximal oxygen uptake (VO(2 max)) assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire score or New York Heart Association scale.


RESULTS
Forty-seven patients (31.9% ischemic, 21.3% hypertensive, 10.6% ischemic and hypertensive, 36.2% idiopathic-dilated cardiomyopathy) were randomly assigned to pentoxifylline 600 mg BID (n=23) or placebo (n=24) if they had a compensated CHF with a LVEF less than or equal to 40% and had taken their standard treatment consisting of angiotensin-converting enzyme inhibitors, diuretics and beta-blockers for at least 3 months. Baseline demographic and clinical characteristics of each group were similar. Forty-one patients completed the study protocol and were analysed for primary and secondary endpoints. After 6 months of treatment, LVEF was unchanged in the pentoxifylline group compared with placebo (29+/-7 to 33+/-10% vs. 27+/-9 to 34+/-9%, respectively, P=NS). Also the secondary endpoints did not significantly change during follow-up.


CONCLUSIONS
Additional treatment with pentoxifylline is neutral with regard to left-ventricular function, inflammatory cytokines and symptoms in patients with ischemic, hypertensive and idiopathic-dilated cardiomyopathy.
Clinic of Internal Medicine I, Friedrich-Schiller-University, Erlanger Allee 101, 07740 Jena, Germany. philipp.bahrmann@med.uni-jena.de
Philipp
P
Bahrmann
Uta M
UM
Hengst
Babara M
BM
Richartz
Hans R
HR
Figulla
D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D010431:Pentoxifylline