Stent Design
- Constant stent’s design provides the advantages of perfect flexibility and good radial strength to CORACTO [2].

Polymer Coating
-CORACTO stent is coated with a very thin layer (4 μm) of bio-absorbable polymer which is loaded with 1.7 μg/mm2 Rapamycin [2, 3].

CORACTO Clinical Performance
- Clinical studies showed that CORACTO performs very successfully in clinically difficult lesions. This is the result of the combination of polymer coating, polymer absorption drug release kinetics and the antiproliferative effect of the drug. In addition bio-absorbability of the polymer eliminates the need for drug usage by the patient [2, 3].

Polymer Features
- Polylactic-co-glycolic acid based copolymer is used as the drug carrier. Since it is biocompatible and bio-absorbable it does not cause an inflammatory reaction in the body. In the body the polymer degrades into lactic acid and glycolic acid which are already present in the body [4, 7, 10, 11].

Polymer Degradation
- Polymer degrades completely into its monomer, following the drug release, which eliminates long term antiplatelet therapy of the patient. This advantage also makes possible the application of this stent for patients who are not supposed to use antiplatelet drugs [2].

Delivery System
- HYDROMERTM HYDROPHILIC coated hypo-tube, proximal shaft and distal shaft provides low friction that enhances trackability and pushability. Low crossing profile provides an excellent lesion crossing.

Drug
- Rapamycin which is used in CORACTO’s coating is a type of immunosuppressive drug. It controls activation and proliferation of the smooth muscle cells by controlling mitosis. The most important characteristic of this drug is preventing proliferation without harming the cells [5].

Rapamycin is used as antiproliferative drug and an active ingredient material of CORACTO. It is a well-known drug used as immunosuppressive agent to prevent restenosis by the inhibition of the activation and proliferation of vascular smooth muscle cells. It basically arrests the mitotic cell cycle at the beginning [5]. Abnormal smooth muscle cell (SMC) proliferation plays a major role in the development of restenosis following Percutaneous Transluminal

Coronary Angioplasty (PTCA) [13]. It is stated that Rapamycin prevents SMC proliferation by blocking cell cycle progression at the G1/S transition [13, 14]. Rapamycin acts by binding the TOR protein kinases, which in turn prevents cell cycle progression by blocking the ability of T cells to proliferate [13, 14, 15].

Figure 1. The effect of Rapamycin on the Cell Cycle [16].

Animal Study and Clinical Trials
Prof. N. Reifart and his team performed a randomized, multicenter clinical trial with a 24 month follow up. 95 patients enrolled in this trial. 89 of 95 patients participated in the follow-up. 86% of the patients had 3 months CTO (chronic total occlusion) and 14% subtotal occlusion. In the control group, 44 patients who enrolled in this trial received their bare-metal stent (BMS) and in the Sirolimus-Eluting Stent (SES) group, 45 patients who enrolled in this trial received their SES. They received a total of 119 and 130 stents respectively. At the end of a 6 month follow-up period, none of the patients who died had a stent thrombosis or a myocardial infarction. In-segment re-occlusion was 7% in control group, whereas it was 0% in the SES group. TVR (Target Vessel Revascularization) results were 54.5% and 11% respectively [2, 3].

- Animal studies showed a complete endothelisation in the following 28 days after the operation [3].

Fig. 1  In a pig-model the SES showed a complete endothelialisation after 28 days with no signs of inflammation [3].

Conclusion

Restenosis is the major problem of the stent angioplasty and it limits its application. Drug eluting stents increases the effectiveness of the operation and the quality of the life of the patient by decreasing restenosis ratio following the angioplasty operation. The CORACTO stent achieves a perfect harmony of polymer and drug to provide the desired drug release profile hence providing timely clinical effect to the patient. In addition, since polymer degrades following the drug release, patients do not require additional long term antiplatelet drug therapy.

References

1. “Restenosis: A Guide to Therapy” edited by David P Faxon, Martin Dunitz Ltd., 2001.
2. N. Reifart, “Design Dossier of CURA; Drug Eluting Stent”.
3. N. Reifart, “CORACTO A Sirolimus-coated stent in CTO”, Bad Soden Germany.
4. R.A. Jain, “The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide) (PLGA) devices.”, Biomaterials 21 (2000) 2475-2490.
5. C. Haery, R. Sachar and S. G. Ellis, “Drug-eluting stents: The beginning of the end of Restenosis?” Cleveland Clinic Journal of Medicine 71 (2004).

*You can request the CE Certicifate from:
regulatory.affairs@alvimedica.com