Drug Eluding Stents- A review of the current technology.
Romeo A. Majano, M.D. (Baptist Health Systems, Florida)
• The talk addresses the problem of in-stent restenosis from the epidemiological and pathophysiological point of view as well as the current state of Drug Eluding Stent technology.
Restenosis is costly
need for repeat PCI, bypass surgery, increased hospitalization, other costs
15% to 20% of patients may undergo repeat PCI within 6 months of initial procedure
5% to 8% undergo CABG
Pathophysiology of Restenosis
Occurs within a period of 6 - 9 months of PCI
Major components:
Elastic Recoil – Occurs within 30 min and up to 24 hrs. Worse in eccentric, ostial lesions and post DCA.
Negative Arterial Remodeling – “constriction” of shrinkage of vessel post PCI. May account up to 85% late lumen loss in DCA/PTCA Neointimal Hyperplasia
• The molecular mechanisms of action of Sirolimus and Placlitaxel are discussed.
• Sirolimus
Dual mechanism of action: antiproliferative and reduces inflammatory cell activity.
Selectivity for proliferating cells and preferential targeting of SMCs via TOR
Cytostatic mode of action
acts before the critical checkpoint in the G1 phase of the cell cycle
Ability to effectively stop proliferation of SMC while allowing normal re-endothelialization to occur
Broad therapeutic window
Highly lipophillic
Long Half life- 62 hours
Sirolimus blended in mixture of nonerodable polymers and then layered (thickness 5 microns) onto a BxVelocity. 140 micrograms/cm2 per unit of metal surface. A layer of drug-free polymer on top to prolong release. 80% of drug eluted within 30 days.
• New molecular mechanism of action of Sirolimus are discussed with original research.
• Paclitaxel acts, at the end of the cycle, by preventing the deconstruction of microtubules
• acts before the critical checkpoint in the G1 phase of the cell cycle
• Ability to effectively stop proliferation of SMC while allowing
• Clinical trials:
• The talk then addresses the current trials and clinical data analyzing and supporting the use of drug eluting stent technology.
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