Trimetazidine Improves the Outcome of EECP Therapy in Patients with Refractory Angina Pectoris

INTRODUCTION: Cardiovascular disease (CAD) associated with death and disability remains a serious medical problem. In some patients the initial clinical coronary artery disease presentation is stable angina pectoris. AIM: The aim of the study was to evaluate the effect of EECP therapy with or without trimetazidine (TMZ) in patients with refractory angina via modulating peripheral monocyte expression of Toll like receptor2 (TLR2) and its downstream signaling. METHODS: This is a double-blind randomized prospective study in which 88 stable refractory angina patients allocated into two groups, Enhanced External Counter Pulsation (EECP) group: included 44 patients with stable refractory angina, and were treated with EECP-Therapy. TMZ-EECP group: included 44 patients with stable refractory angina, we gave TMZ 35 mg twice daily in addition to EECP-Therapy. RESULTS: TLR2 expression in peripheral monocyte investigated by flow cytometry and 8-iso-prostaglandin F2β (8-iso-PGF2 β), interleukin1β (IL-1β), heat shock protein 60 (HSP60) and monocytes chemoattractant protein-1(MCP-1) were also measured before the EECP-therapy and before giving TMZ to patients, and after 35 hours of EECP treatment (7 consecutive weeks). Inhibition in TLR2 expression in peripheral monocyte was observed among the EECP group (P<0.05). Inflammatory cytokine MCP-1 was remarkably decreased in both study groups but (heat shock protein 60 (HSP60), MCP-1 and interleukin-1β (IL-1β)) significantly decreased levels were observed among the TMZ-EECP group (P<0.05). Also, the oxidative stress biomarker 8-iso-prostaglandin F2β (8-iso-PGF2β) was decreased in both study groups but significantly decreased levels were observed among the TMZ-EECP group (P<0.05). TMZ and EECP therapy in patients with stable refractory angina remarkably decreased the inflammatory markers HSP60, MCP-1 and IL-1β in serum levels also the decreased levels were found in serum levels of oxidative stress marker 8-iso-PGF2β serum level. CONCLUSION: EECP-therapy decreased the expression of TLR2 on peripheral monocytes in patients with chronic stable refractory angina which yield improvement in the quality of patients’ life by decreasing the frequency of angina episodes, decreasing the Short-acting nitrate use and change the exercise tolerance and distance.