Abstract 811: Pentoxifylline Reduces Proinflammatory and Increases Antiinflammatory Activity in Patients with Coronary Artery Disease - A Randomized Placebo-Controlled Study
Background: The balance between different immunological stimuli is essential in the pathophysiology, progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease.
Objectives: We sought to determine whether prolonged treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the proinflammatory response observed in patients with acute coronary syndromes (ACS) and increase antiinflammatory activity.
Methods: In a double-blind, prospective, placebo-controlled study, 64 patients with non-ST-elevation ACS were treated with an early invasive strategy and randomized to receive pentoxifylline 400mg TID or placebo for six months. Patients had blood samples collected at baseline, 1 month and 6 months for the analysis of the proinflammatory markers C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the antiinflammatory cytokines transforming growth factor (TGF)-beta1 and IL-10.
Results: Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months of treatment (P=0.04 and P<0.01 respectively). IL-12 levels were higher on both groups after 6 months but the increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the antiinflammatory cytokine IL-10 also declined less significantly in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a higher increase in the levels of TGF-beta1 in the former group (P=0.16). At 6 months, four patients (13%) in the pentoxifylline group experienced one of the events in the pre-specified composite endpoint of death, nonfatal infarction or urgent rehospitalization for an ACS compared to 11 patients (34%) in the placebo arm. The Kaplan Meier curve for the combined endpoint demonstrated the beneficial use of pentoxifylline, with a significant difference among the groups (P=0.04).
Conclusions: Pentoxifylline reduces proinflammatory and increases antiinflammatory response in patients with coronary artery disease and may have beneficial clinical effects on cardiovascular events.