MECHANISMS AND THERAPEUTIC CONCEPTS OF RE STENOSIS AFTER STENT IMPLANTATION

Demonstration of a reduced restenosis rate after stent implantation (B enestent, STRESS) has initiated rapid increase in stent implantation r ates with widening indications. At present, the majority of stents are implanted in ''none-Benestent/STRESS-lesions'' with the consequence o f a higher restenosis rate as previously expected. Stent restenosis ha s therefore become a relevant problem in interventional cardiology. In contrast to balloon angioplasty, where acute and subacute recoil repr esents the major mechanism of restenosis, stent restenosis is exclusiv ely attributed to neointima proliferation. Morphological studies have demonstrated that neointima is caused by early smooth muscle cell ingr owth with a maximum after 7 days which is then gradually replaced by e xtracellular matrix. Systematic clinical, angiographic and intravascul ar ultrasound studies have identified several risk factors for increas ed stent restenosis such as: diabetes mellitus, treatment of restenosi s. serial stent implantation, small and calcified vessels, ostial lesi ons, venous bypass grafts and complex stenosis morphology. In addition , there is increasing evidence that aggressive implantation techniques with high pressures and oversized balloons may also induce higher res tenosis rates. Optimal treatment of instent restenosis has not been de termined so far. Balloon angioplasty is at present considered the ther apeutic option of choice. Several small studies have shown, that in sh ort, discrete lesions (< 10 mm) results of simple PTCA are acceptable with re-restenosis rates between 15 and 35%. The intervention is consi dered safe with low complication rates. In 10 to 15% additional stent implantation is necessary. usually due to dissections proximal or dist al to the treated stent. In long, diffuse stent restenosis (greater th an or equal to 10 mm), however, PTCA results in high re-restenosis rat es up to > 80%. This is most likely due to insufficient early balloon angioplasty results with minimal luminal diameters (MLD) significantly below the previous stent diameter. Therefore, debulking techniques ha ve been used to reduce neointima burden within the stent. At present 3 techniques are available: directional coronary atherectomy (DCA), Exc imerlaser angioplasty (ELCA) or high frequency rotablation. All of the se techniques achieve a significant reduction in plaque volume within the stent and in combination with balloon angioplasty allow larger MLD s than PTCA alone. Limited experiences with ELCA and rotablation have shown that the techniques are safe without major periinterventional co mplications. DCA, however, has been accompanied with stent destruction and therefore should be considered with large care, especially in ste nts with coil design. At present, no randomized controlled trials for the comparison of debulking techniques with or without balloon angiopl asty versus balloon angioplasty alone are available. Three multicenter trials have been initiated (LAPS, ARTIST and TWISTER) to compare debu lking techniques versus balloon angioplasty in diffuse stent restenosi s. Adjunct medical treatment after interventions for stent restenosis is usually limited to ASS alone, indications for additional applicatio n of Ticlopidine have not been verified so far. Positive results are e xpected for the use of local radiation therapy either by radioactive s tent implantation or after-loading techniques. With increasing stent i mplantation rates and indications, about 400 000 stents will be implan ted in 1997 worldwide. Considering a low restenosis rate of 20%, 80 00 0 stent restenosis will occur within one year. Final recommendations f or optimal treatment of these patients are not yet available.