Future challenges for DES

Professor Jean Marco of the interventional cardiology unit at Clinique Pasteur, Toulouse, France, presented on challenges in clinical practice with DES. He discussed how increasing the lesion/patient complexity meant a greater chance of procedural failure and early or late complication.

Marco suggested the main reasons for DES failure in complex patients/lesions could be inadequate release of antiproliferative agent into vessel wall, physical properties of the polymer, coating integrity and release rate kinetics, vascular biocompatibility of the polymer and inefficacity of the drug.

Professor Joachim Schofer of Hamburg University Cardiovascular Centre, also discussed challenges in clinical practice with DES. He presented on how major clinical trials of the (polymer-based) sirolimus and paclitaxel-eluting stents have unequivocally demonstrated the angiographic and clinical efficacy of either stent. However, treatment of certain complex patient and lesion subsets may result in an unsatisfactory clinical outcome, he said. Schofer added that late stent thrombosis is as yet an unresolved issue of concern and that procedural and technological modifications may aid in improving clinical efficacy and long-term safety of DES.

Dr Bernard De Bruyne of the Cardiovascular Center Aalst, Belgium, presented on 'vulnerable plaques: will we be stenting?'. He discussed a plan of investigations, beginning with to establish biological, pathological, and mechanical features of the vulnerable plaque. Following that: to develop invasive and noninvasive tools to detect the vulnerable plaque; to test the performance of these tools to identify these key features in plaques that have just caused acute coronary syndrome; to look for the presence of vulnerable plaque elsewhere in the same patient; to establish the natural history of high-risk plaque; to establish the potential impact of such findings on the procedural strategy and short-term outcome; and to test systemic and/or local therapies aimed at improving the natural history to prevent infarction and sudden death.

Dr Renu Virmani of the CVPath, International Registry of Pathology, Gaithersburg, US, presented on the polymer preclinical experience as a predictor of the clinical results. She discussed how the current generation of DES, especially Taxus, show greater fibrin deposition (delayed healing) and poor endothelialization in animal models. In "real-world" patients, she said DES have greater tendency for thrombosis, especially Taxus, and that it is believed a newer generation of polymer and/or drugs are needed for the prevention of restenosis. Virmani said the Xience V stent in preclinical studies shows promise with greater endothelialization while maintaining low profile, good deployment characteristics and minimal neointimal formation in rabbits and pig arteries.

Virmani also discussed new experimental data on polymeric carriers, in a earlier session at PCR titled 'Preparing for the next generation of DES'. She concluded that sirolimus analogs may hold superiority to paclitaxel based DES stents and that better, more compatible polymeric carriers are the answer to future improvements in DES stents.

Chair of the session, Professor Bernard Chevalier of the Centre Cardiologique du Nord, Saint-Denis, France, began by asking what was being waited for in a second generation DES. He said mechanical features included excellent deliverability, appropriate radio-opacity - stent overlapping, and good side branch access/patency. Desirable biocompatibility features were subacute (no inflammation and no webbing effect for side branch patency) and late (no late thrombosis - increased safety profile and extended indications) properties.

Chevalier also presented on 'ZoMaxx: Global and Clinical Programme Development' during the session. ZoMaxx I is designed as a prospective, randomized, two-arm, controlled multicentre trial with 400 patients being treated with the ZoMaxx or TAXUS stents. Clinical follow-up will be held at one, six, nine and 12 months post-procedure and annually for five years. There will also be nine-month angiographic follow-up for all patients and nine-month IVUS follow-up for the first 250 patients. The primary endpoint is in-segment late-loss at nine months (as measured by QCA), defined as the difference between the post-procedure minimal lumen diameter (MLD) and the follow-up angiography MLD. Secondary endpoints include MACE at 30 days, six, nine, and 12 months, and annually, thereafter, through five years. Also, TLR, TVR and TVF at nine months, angiographic in-stent and in-segment binary restenosis at nine months and angiographic in-stent late loss.

The ZoMaxx II study is designed as a prospective, multi-center, randomised, two-arm controlled non-inferiority trial, with 1,670 patients, treated with the ZoMaxx or TAXUS stents. Clinical follow-up will be the same as in ZOMAXX 1, with nine-month angiographic follow-up for 836 (50%) of patients and nine-month IVUS follow-up for the first 400 patients. Primary endpoints are TVR at nine months, with the major secondary endpoint being in-segment late loss at nine months. Additional secondary endpoints include MACE at 30 days, six, nine and 12 months, and annually, thereafter, through five years.

Dr Alexandre Abizaid of the Instituto, Dante Pazzanese, De Cardiologia presented initial clinical results of the novel multimaterial TriMaxx Stent. He said based on the initial clinical experience at a single site, the stent had a very low profile (strut thickness of 0.0029"), ideal radiopacity, excellent flexibility and conformability, high procedural success and acceptable six months clinical (6% TVR) and angiographic (22% restenosis) results.