Bioresorbable vascular scaffolds for the treatment of coronary artery disease: what have we learned from randomized-controlled clinical trials?

Although current everolimus-eluting coronary stents have shown improved event-free survival within the first year following implantation compared with bare-metal stents or earlier generation drug-eluting stents, they remain associated with an ongoing risk for adverse outcomes (thrombosis, myocardial infarction, and restenosis) beyond 1 year at rates similar to those observed following bare-metal stent deployment. This ongoing very late hazard has been attributed to the permanent presence of the metal frame and/or polymer in these stents. The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) has been developed to provide mechanical support and drug-delivery functions similar to metallic drug-eluting stents, followed by complete resorption with recovery of more normal vascular structure and function, thus avoiding the limitations associated with permanent metallic endovascular prostheses. Absorb BVS has shown safety and efficacy in the dedicated clinical trial development program of Abbott Vascular and in an array of investigator-sponsored studies involving a broad spectrum of clinical (patient) as well as coronary anatomic complexity. Longer-term evidence, largely limited to single-arm studies, appears to reflect durable safety and efficacy and suggests Absorb BVS to be an attractive therapeutic option. Interim evidence from a series of randomized-clinical trials (RCTs) comparing Absorb BVS with the Xience cobalt-chromium metallic everolimus-eluting stent has shown noninferiority of Absorb BVS with respect to target lesion failure (composite occurrence of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization) beyond the first year, with no statistically significant differences in other safety/efficacy measures. However, concerns do exist in terms of increased rates of scaffold thrombosis, the risk for which may be mitigated by improved patient and lesion selection, procedural technique, and device iteration. We provide an overview of the evolution of percutaneous coronary intervention, in-vivo characterization of Absorb BVS resorption, and a summary with a critical evaluation of available evidence from RCTs, pooled analyses, and meta-analyses of RCTs for the safety and efficacy of Absorb BVS obtained primarily following the treatment of noncomplex coronary lesions in patients with stable ischemic heart disease and/or stabilized acute coronary syndromes.

Interventional Management of Unprotected Left Main Coronary Artery Disease: Patient Selection and Technique Optimization.

For many years, coronary artery bypass graft surgery has been the gold standard for revascularization of patients with left main disease; however, increasing evidence suggests that percutaneous coronary intervention with drug-eluting stents may be an acceptable alternative or even preferred in select cases. This review will present clinical evidence examining the outcomes of drug-eluting stents compared to coronary artery bypass graft surgery for unprotected left main coronary artery disease and discuss the anatomic factors, patient variables, and clinical strategies that may dictate choice of revascularization modality for patients with left main disease. If percutaneous coronary intervention is selected to treat unprotected left main disease, meticulous technique is essential to optimize outcomes, including use of procedural physiology and imaging guidance, optimal stent and adjunct pharmacology use, and expert management of the distal bifurcation. Finally, issues of equipoise and uncertainty are identified, representing areas for future investigation.

Xience side branch access stent for treatment of bifurcation coronary disease: a review of preclinical data.

The Xience Side Branch Access (SBA) stent is an everolimus-eluting stent designed specifically for branching coronary geometry, providing wire access into the side branch (SB) regardless of the planned treatment strategy. The stent is delivered via a low-profile, dual-lumen, and single-tip catheter. A single inflation deploys the stent in the main branch (MB) and opens a portal into the SB. It is through this portal opening, allowing wire access into the SB, that this device differentiates itself from certain other dedicated bifurcation devices currently in various stages of development and testing. The Xience SBA stent was compared with a standard Multi-Link Vision® stent using a provisional T-stenting strategy in an ovine beating heart model. The Xience SBA stent tended to be deployed with less mean contrast usage (21.05 vs. 43.23 mL; P = 0.09), shorter fluoroscopy time (2.55 vs. 4.52 minute; P = 0.12), and lower rates of guidewire entanglement (16% vs. 100%) compared with the workhorse stent. As a result, the total procedure time with the Xience SBA stent was significantly shorter than that with the standard stent (5.46 vs. 8.65 minute; P = 0.01). The Xience SBA stent was also evaluated by four recently trained interventionalists who had no previous experience with the device. Using a perfused synthetic heart model, SB access time was reduced by 54%, average fluoroscopy time was reduced by 46%, and average contrast usage was lowered by 39% with the Xience SBA compared with the standard stent. Initial experience in the ovine model suggests that the Xience SBA stent is also amenable for use in distal left main coronary artery disease, regardless of whether it is deployed in the left ascending coronary artery or left circumflex artery and the portal opened in the opposing vessel. On the basis of these experimental results, the Xience SBA stent is an easy to use and versatile device for the purpose of SB access and potentially for the treatment of bifurcation coronary artery lesions.

Dedicated bifurcation devices.

Coronary bifurcation lesions are a common challenge for interventional cardiologists, for which there is no clear consensus on optimal treatment. The side branch (SB) ostium has become the focus of new treatment strategies because it is a common site of restenosis. In comparison, restenosis and reintervention rates in the main branch are acceptably low, reflecting improved techniques and greater use of drug-eluting stents. Many different companies are evaluating dedicated bifurcation devices that are designed to offer easy access to the SB, but that differ in concept and in the degree of coverage provided to the SB ostium. Some are bare metal stents, whereas several are drug-eluting iterations based on platforms used in conventional stents. The promise of these dedicated bifurcation devices is illustrated by early results from single-arm clinical studies.

Assessing the landscape of stent thrombosis: the drug-eluting versus bare-metal stent controversy.

Within labeled indications, drug-eluting stents (DES) are as safe as bare-metal stents (BMS). Data from key randomized, controlled trials comparing paclitaxel-eluting stents with BMS or sirolimus-eluting stents with BMS show no difference in risk of death/myocardial infarction or stent thrombosis using uniform definitions of stent thrombosis. However, these trials and other analyses indicate a difference in time distribution of stent thrombosis, with more cases of stent thrombosis occurring later (ie, after 1 year) in patients with DES--a problem to which the lack of adequate antiplatelet therapy appears to be a main contributor. A consistent finding from randomized, controlled trials of DES versus BMS is the significantly reduced need for reintervention associated with DES use. In the absence of any other differences in safety between DES and BMS, this reduced need for reintervention constitutes a significant advantage for DES in clinical practice.

Bifurcation coronary artery disease: current techniques and future directions (part 1).

The treatment of bifurcation coronary artery disease is a common challenge facing the interventional cardiologist. There have been major advances in techniques as well as more widespread use of drug-eluting stents; both appear to have contributed to the realization of single-digit target lesion revascularization rates as well as improvement in short-term complications such as stent thrombosis. Adequate treatment of the side branch ostium, the site most frequently described as being susceptible to restenosis, has become the focus of newer bifurcation techniques as well as dedicated devices for the treatment of this complex lesion subset. Since main branch reintervention rates are sufficiently low and silent restenosis of the side branch ostium is an all-too-common finding, there is no clear consensus on the optimal treatment strategy for bifurcation coronary disease. The following is a comprehensive review of those commonly used techniques as well as dedicated devices currently under development for the treatment of bifurcation coronary artery disease.

Balloon alignment T-stenting for bifurcation coronary artery disease using the sirolimus-eluting stent.

OBJECTIVE: The purpose of this study was to evaluate the long-term outcomes of bifurcation coronary lesions treated with a novel technique called "balloon alignment T-stenting". BACKGROUND: The optimal technique for the treatment of bifurcation coronary disease has not yet been established. METHODS: Twenty-six patients with bifurcation coronary lesions were treated with currently available drug-eluting stent (DES) platforms. This was a pilot study to determine the long-term efficacy of a novel technique, "balloon alignment T-stenting". Based on this technique we performed 6-month anniversary angiography to determine restenosis rates for both main and side branch lesions treated. RESULTS: Twenty-six main branches and 27 side branches were treated with this novel technique. Angiographic 6-month follow up was available for all 26 patients treated. There were no postprocedural mortalities and no cases of postprocedural stent thrombosis during the follow-up period. At 6-month anniversary angiography, no evidence of main branch restenosis was seen. However, there were 2 cases of side branch restenosis for a total side branch restenosis rate of 7.4%. Target lesion revascularization for the 26 patients in the study was 7.6%. The total major adverse cardiac event rate for the group as a whole was 15.4%, with 2 periprocedural non-Q-wave myocardial infarctions and 2 target lesions requiring revascularization at 6 months. CONCLUSION: Using currently available DES platforms, the data compiled from this small, single-center pilot study suggest that balloon alignment T-stenting may represent a reasonable approach for the treatment of bifurcation coronary artery disease. However, more comprehensive, larger-scale trials will be required to validate these preliminary findings.

Promising though not yet proven: emerging strategies to promote myocardial salvage.

Remarkable advances in our ability to achieve early and sustained culprit vessel patency in acute myocardial infarction have been satisfying, but our enthusiasm must be tempered by the knowledge that the overall treatment strategy often leaves an inadequate long term clinical result. Early success of percutaneous therapy as judged at angiography does not ensure recovery of normal left ventricular function, the most important determinant of survival in acute myocardial infarction. That congestive heart failure and death still complicate apparently successful percutaneous procedures underscores the need to develop novel therapies which salvage jeopardized myocardium, limit infarct size and preserve left ventricular function. An ever-increasing body of data demonstrates a multifactorial mechanism of myocyte injury and microvascular collapse and also demonstrates that these injuries seem to have a profound impact on long-term outcomes. Given these findings, microvascular protection during the acute event has become the focus of a variety of emerging technologies. The goal of these mechanical and pharmacologic therapies is the restoration of normal metabolic function at the myocyte level. The acute pathologic mechanisms which contribute to sustained left ventricular dysfunction despite angiographically successful revascularization will be reviewed as will be several strategies being developed to counter these pathologic mechanisms.