[Pathophysiology and therapeutic concepts in coronary restenosis]

Demonstration of a reduced restenosis rate after stent implantation (Benestent, STRESS) has initiated rapid increase in stent implantation rates with widening indications. At present, the majority of stents are implanted in "none-Benestent/STRESS-lesions" with the consequence of a higher restenosis rate as previously expected. Stent restenosis has therefore become a relevant problem in interventional cardiology. In contrast to balloon angioplasty, where acute and subacute recoil represents the major mechanism of restenosis, stent restenosis is exclusively attributed to neointima proliferation. Morphological studies have demonstrated that neointima is caused by early smooth muscle cell ingrowth with a maximum after 7 days which is then gradually replaced by extracellular matrix. Systematic clinical, angiographic and intravascular ultrasound studies have identified several risk factors for increased stent restenosis such as: diabetes mellitus, treatment of restenosis, serial stent implantation, small and calcified vessels, ostial lesions, 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 restenosis rates. Optimal treatment of instent restenosis has not been determined so far. Balloon angioplasty is at present considered the therapeutic option of choice. Several small studies have shown, that in short, discrete lesions (< 10 mm) results of simple PTCA are acceptable with re-restenosis rates between 15 and 35%. The intervention is considered safe with low complication rates. In 10 to 15% additional stent implantation is necessary, usually due to dissections proximal or distal to the treated stent. In long, diffuse stent restenosis (> or = 10 mm), however, PTCA results in high re-restenosis rates 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 have been used to reduce neointima burden within the stent. At present 3 techniques are available: directional coronary atherectomy (DCA), Excimerlaser angioplasty (ELCA) or high frequency rotablation. All of these techniques achieve a significant reduction in plaque volume within the stent and in combination with balloon angioplasty allow larger MLDs than PTCA alone. Limited experiences with ELCA and rotablation have shown that the techniques are safe without major periinterventional complications. DCA, however, has been accompanied with stent destruction and therefore should be considered with large care, especially in stents with coil design. At present, no randomized controlled trials for the comparison of debulking techniques with or without balloon angioplasty versus balloon angioplasty alone are available. Three multicenter trials have been initiated (LARS, ARTIST and TWISTER) to compare debulking techniques versus balloon angioplasty in diffuse stent restenosis. Adjunct medical treatment after interventions for stent restenosis is usually limited to ASS alone, indications for additional application of Ticlopidine have not been verified so far. Positive results are expected for the use of local radiation therapy either by radioactive stent implantation or afterloading techniques. With increasing stent implantation rates and indications, about 400,000 stents will be implanted in 1997 worldwide. Considering a low restenosis rate of 20%, 80,000 stent restenosis will occur within one year. Final recommendations for optimal treatment of these patients are not yet available.