Drug-eluting stents (DES) have considerably reduced neointimal hyperplasia and significantly decreased the risk of restenosis compared to bare metal stents (BMS) . However, the persistent polymer within the vessel lumen has been held responsible for ongoing endothelial inflammation, incomplete endothelialization and subsequent atherosclerosis, all leading to late complications such as restenosis and stent thrombosis .
Everolimus-eluting stents (EES) and biolimus-eluting stents (BES) are more recent DES that have been widely investigated. The EES is at present the most frequently used DES in the USA and in Europe . It was demonstrated as non-inferior to sirolimus-eluting stents (SES) in the ISAR-TEST IV and the EXCELLENT trial and superior to paclitaxel eluting stents (PES) in two large randomized studies (Spirit-IV and COMPARE) [4–7]. One propensity score matched registry (LESSON-1) showed a trend towards a lower risk of death, myocardial infarction (MI) and target-vessel revascularization (TVR) as compared to SES over a 3-year follow-up .
BES differs from EES in that it possesses an abluminal polymer coating that is completely converted to lactic acid in 6 months and, via the Krebs cycle, to carbon dioxide and water in 6 to 9 months. Two large clinical trials (NOBORI and LEADERS) proved its non-inferiority to PES and SES at 9 months and 4 years, respectively [9, 10]. The propensity score matched EVERBIO trial showed similar risk of death, MI and TVR in BES compared to EES during a 2-year follow-up . Recently, the randomized COMPARE II trial enrolling 2,707 patients, confirmed the BES safety but no differences were observed in clinical endpoints at 2-year follow-up when compared to EES . The ongoing Global LEADERS trial with an expected inclusion of >10,000 patients will provide further information on BES. The lactic acidification of the media from the polymer could impact vascular healing at the stent vicinity and promote a deleterious inflammatory reaction .
The unresolved problem of neointimal proliferation and very late stent thrombosis from lingering polymers and vascular scaffolds, led to the development of new-generation completely resorbable stents. The Absorb™ (Abbott Vascular, Abbott Park, IL, USA) is the first CE approved DES with a bioresorbable vascular scaffold (BVS). It uses a poly-l-lactide polymer that is absorbed after approximately 2 years via the Krebs cycle. A prospective, open-label, 2-stage study called ABSORB including 131 patients was conducted in Europe and New Zealand and led to its approval by the EU in January 2011 for the treatment of coronary artery lesions . The major adverse cardiac event (MACE) rate was reported as 6.8% at 2-years follow-up and late lumen loss (LLL) 0.27 mm at 12 months [15, 16]. Its non-inferiority to the Xience Prime (Abbott Vascular), an EES, is currently under investigation in the international ABSORB EXTEND trial that plans to enroll 1,000 patients (NCT01023789). To date, there is no data on BVS compared to EES or BES, and independent trials are eagerly awaited. We seek to compare the efficacy and safety profiles of these three different types and generations of DES.
Study objectives and hypothesis
The purpose of the EVERBIO II trial is to evaluate the efficacy, angiographic outcome and safety of three different stents in de novo coronary artery lesions: the BVS Absorb™ (Abbott Vascular), the EES Promus Element™ (Boston Scientific, Natick, MA, USA) and the BES Biomatrix Flex™ (Biosensors International Ltd., Morges, Switzerland). The null hypothesis to be rejected is that all three stents are of equal efficacy. We believe there will be a significant difference with regard to LLL at 9 months and a clinical endpoint of death, MI and TVR at 12 months between EES and BES and BVS stents.