Comparison of Efficiency of High Dose Atorvastatin and Endothelial Progenitor-Capture Stents and Bare Metal Stents in Reduction of Neointimal Formation in Patients With Non ST-Segment Elevation Acute Coronary Syndromes

The short and long-term efficiency of PCI is limited to in-stent restenosis (ISR) and stent thrombosis. Expansion of the stent in the target artery induces local injury of the vessel wall, primarily from the disruption of the endothelial lining. Following the injury, the reparatory mechanisms are activated leading to recovery of the endothelial coverage over the stent struts. Disruption of the endothelium causes the activation and adherence of platelets (minutes-hours) and recruitment of the monocytes and leukocytes (hours to days). The time that elapses between the endothelial disruption caused by the expanded stent and full coverage of the struts with new endothelial cells carries the highest risk of in-stent thrombosis.

During this same time frame, the initial events of ISR occur, - primarily migration and proliferation of smooth muscle cells. The key event in rebuilding the endothelial layer over the stent struts is the recruitment of circulating endothelial progenitor cells (EPC), their adherence and attachment to the surface of the stent and vascular wall between the struts. The full coverage of the prothrombotic metal struts with new endothelial cells reduces the initially high risk of thrombosis. The repair processes are completed after 1 month when bare metal stents are used, and over 6 months after DES implantation.

The course of events is different after implantation of drug-eluting stents. Recruitment of the inflammatory cells as well as smooth muscle cells is reduced and slowed. This effect is associated with a reduced potential for neointima formation (ISR), but also with an unfavorable lag in reendothelialisation.

As shown in studies using angioscopy, thrombus formation over the DES struts can be seen as long as 6 months after PCI. The effect is probably caused by the inhibitory effects of immunosuppressive, antimitotic and antiinflammatory drug released from the stent on the EPCs adhering to the place of vascular injury and the struts. The use of DES significantly reduced the risk of ISR, but the slowing and prolongation of the reparatory process may increase the risk of the late in-stent thrombosis as well as other unwanted effects, such as edge effect and formation of the coronary aneurysms. The risk of late thrombotic effects of DES is mainly associated with discontinuation of dual antiplatelet therapy, therefore the treatment should be continued for at least 12 months or even indefinitely. The following groups of patients have a particularly high risk of in-stent thrombosis: acute coronary syndromes, cardiogenic shock, diabetes, procedure-related parameters (coronary dissection, long lesion, small vessel diameter, use of multiple stents). On the other hand, prolonged dual anti-platelet therapy is associated with significant risk (bleeding, thrombocytopenia) especially in patients with peptic ulcer disease and in the elderly. Discontinuation of this therapy is also indicated in patients undergoing surgery, which may increase the risk of thrombotic events.

The concept of EPC-capture stents. Numerous studies have shown that circulating EPCs contribute to the repair of the endothelium after injury, most likely by repopulating the site of stent implantation. The number of circulating EPCs is considered a marker of the turnover of the endothelium, as well as a promising marker of the cardiovascular risk. EPCs can be identified by the presence of surface markers - CD34, CD133 - or vascular endothelial growth factor type 2 receptor (VEGFR2) which can be identified using labeled monoclonal antibodies. Since EPCs represent a pool of cells which contribute to the endothelial repair after vascular injury, the increased homing and retention of these cells at the site of stent implantation may increase and speed up the process of endothelisation.