Target Lesion Revascularization in the NORSTENT Trial

Abstract

Multicenter randomized clinical trials with no disclosures and an excellent design and statistic analysis such as the NORSTENT (Norwegian Coronary Stent Trial) are only sporadically found. Therefore, data coming from such a study are a helpful instrument in guiding clinical practice and shedding light on previously unclear issues.In the NORSTENT [1], 9,013 patients were randomized to receive either drug-eluting stents (DES) or bare metal stents (BMS). At the time the trial was designed, there were major concerns regarding the safety of DES because of the potentially increased risk for stent thrombosis. After 5 years of follow-up, there were no significant differences between groups in the primary composite outcome of death from any cause or nonfatal spontaneous myocardial infarction, as well as in the individual endpoints of myocardial infarction or unstable angina. Measures of quality of life did not differ. During the 5 years of follow-up, "any repeat revascularization" occurred in 19.8% of the patients in the BMS group versus 16.5% of the patients in the DES group (3.3% absolute risk reduction; p < 0.001). The difference was driven by less restenosis with DES.Due to previous criticism (the first results had total revascularization and not target lesion revascularization [TLR] as a secondary endpoint), these newly presented data were highly anticipated. DES resulted in a stable reduction of TLR (TLR with DES: 3.5%; TLR with BMS: 7.6%; p < 0.001) in the first 500 days after implantation, and this effect was consistent in all clinical scenarios and among all clinical risk factors for coronary heart disease, confirming in this way the results of the first publication [1]. This effect was limited in time to the first 2 years, but there was no evidence of a later rebound during the 5-year follow-up.Taking into account the mechanisms of in-stent restenosis (ISR) requiring TLR, these results come as no surprise. Biological, arterial, and stent-related factors are contributing to TLR following similar but not identical mechanisms after BMS and after DES implantation. Neointimal hyperplasia has been classically observed as a major factor for ISR and TLR, especially in the first 6-15 months following BMS implantation [2], which led to the development of the first generation of DES. Safety concerns were raised about these first-generation DES (regarding hypersensitivity reactions to their polymer, evidence of chronic inflammatory reactions, and early neoatherosclerosis [2]), leading to the development of the second generation of DES with thinner struts, longer drug release, and a biocompatible/biodegradable polymer [3]. Their improved technology seems to induce a