Long-term protective effects of the angiotensin-receptor blocker telmisartan on epirubucin-induced inflammation, oxidative stress, and myocardial dysfunction.

Abstract

9030 Background: Chronic inflammation, oxidative stress and renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX): telmisartan (Tel), an antagonist of angiotensin II type-1 receptor, has shown to be able to reduce anthracycline (ANT)-induced CTX. Methods: We carried out a phase II placebo-controlled randomized trial, to assess the possible role of Tel in the prevention of the cardiac sub-clinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI- based treatment, were randomized to one of two arms: Tel n=25; Placebo (PLA) n=24. A conventional echocardiography equipped with Tissue Doppler Imaging, Strain and Strain Rate was performed as well as serum levels of proinflammatory cytokines IL-6 and TNF-a and oxidative stress parameters reactive oxygen species (ROS) and glutathione peroxidase (GPx). All assessments were carried out at baseline, every 100 mg/m2 of EPI dose and at 3, 6 and 12 month-follow up (FU). Results: A reduction of the SR peak comparable between the two arms was observed at the dose of 200 mg/m2 EPI, whereas, at 300 and 400 EPI doses, the SR turned out to increase reaching the normal range only in the Tel arm. The differences between SR changes in the PLA and Tel arm were significant from t3 up to 12 month-FU. Serum levels of IL-6 increased significantly in the PLA arm at t2 in comparison to baseline but remained unchanged in the Tel arm. The same trend was shown by ROS levels which significantly increased at t2 versus baseline in the PLA arm, whilst remained unchanged in the Tel arm. The mean change of ROS and IL-6 at t2 was significantly different between the 2 arms. In the present study, we confirm at 3 month-FU the trend toward a decrease of ROS and IL-6 from t2 in the PLA arm. Conclusions: Our results suggest that Tel is able to prevent not only the acute (early) but even the late (up to 12 month-FU) EPI-induced myocardial dysfunction. These effects are likely to be due to different mechanisms: RAS blockade and prevention of chronic inflammation/oxidative stress.