Abstract 17680: Long Term Effects of Telmisartan on the Inflammation, Oxidative Stress and Myocardial Impairment Induced by Epirubucin.
Introduction: Oxidative stress and Renin-Angiotestin Aldosterone system (SRAA) play a significant role in chemio-induced cardiotoxicity (CTX); telmisartan (Tel), an antagonist of the type II angiotensin receptor, has shown to be able to reduce anthracyclines (ANT) induced CTX. Method and Material. We have carried out a phase II study, controlled with placebo (PLA), to assess the possible role of Tel in the prevention of the cardiac sub-clinical damage induced by the epirubicin (EPI). 49 patients have been recruited (Tel n=25; PLA n=24) (average age ±DS 56±7 years) free from cardiovascular disease, affected by cancer at different sites, candidate to receive EPI based treatment. A conventional echocardiography with Tissue Doppler (TDI), Strain (S) and Strain Rate (SR) imaging was performed. Moreover, serum levels of reactive oxygen species (ROS) and of antioxidants as glutathione peroxidase (GPx) have been dosed. Such assessments have been carried out at the baseline, every 100 mg/m2 of cumulative dose of Epi during the treatment and at the follow up (FU) after 6 and 12 months from the end of the therapy.
Results: A reduction of the SR peak turned out to be comparable between Tel and PLA at the cumulative dose of 200 mg/m2 of Epi (1.45±0.33 s−1 vs 1.54±0.35 s-1; NS); although, with higher cumulative doses of EPI a significant difference was noted between the two treatments, with a mitigation of the peak reduction SR induced by Tel rather than PLA (1.74±0.27 s−1 vs 1.38±0.24 s−1; p<0.001) after 400 mg/m2 of EPI. This difference between PLA and TEL continued to be significant even at the FU at 6 and 12 months (1.77±0.35 s−1 vs 1.50±0.23 s−1; p<0.01). ROS levels have significantly increased after 200 mg/m2 of EPI compared to baseline after PLA (407.3±126 FORT-U vs 518±65 FORT-U; p<0.05), but not in Tel arm (457±61 FORT-U vs 402.6±148 FORT-U; NS). At the third month of FU both ROS and GPx normalized in both arms, continuing to be normal even at the 12th month FU.
Conclusions: Our data suggest that Tel is able to mitigate the effects of CTX precociously induced by the treatment with EPI and to preserve such protective efficiency even after the end of the antiblastic treatment. Such effects are likely to be due to a double action: the block of the SRAA and the reduction of the oxidative stress.
- © 2010 by American Heart Association, Inc.