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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.org)

Volume 8, Supplement 1, 2007

Volume 8, Supplement 1, 2007

Table of Contents

Neointimal Formation Following Drug-Eluting Stents: Physiology, Timeline, and the Influence of Drug Delivery Systems Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis
Percutaneous coronary intervention with drug-eluting stents (DES) is currently the preferred approach to the treatment of obstructive coronary artery disease. Large, randomized trials have demonstrated a significant reduction in the incidence of restenosis and the need for target vessel revascularization following implantation of DES compared with bare-metal stents. Follow-up data extending out to 2 to 4 years have demonstrated efficacy in maintaining luminal patency, but recent concerns regarding potential late adverse effects with DES have been raised. These include aneurysm formation and hypersensitivity reactions, as well as subacute and late stent thrombosis requiring compliance with antiplatelet therapy for protracted periods of time. Evolving strategies to mitigate late adverse events with DES include acceleration of endothelialization, gene therapy targeting pro-healing pathways (ie, nitric oxide donors), smooth muscle cell growth inhibitors, bioabsorbable metal and polymeric stents, and concurrent use of local as well as systemic chemotherapy. [Rev Cardiovasc Med. 2007;8(suppl 1):S3-S10]
Incidence of Late Stent Thrombosis With Bare-Metal, Sirolimus, and Paclitaxel Stents Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis
Stent thrombosis has become a major concern for interventional cardiology. Although infrequent, it is associated with significant morbidity and mortality. Recent attention has focused on the frequency of this complication with drug-eluting stents compared with bare-metal stents in regard to the timing (early, late, or very late) of the event, underlying mechanisms involved, and preventive strategies. Although dual antiplatelet therapy (aspirin plus thienopyridine) is crucial in mitigating the problem, there are significant issues with this management strategy, including the duration of dual antiplatelet treatment, patient compliance, variability in individual response to therapy, bleeding risk, and management of subsequent noncardiac surgical procedures. Newer strategies being evaluated to enhance the safety of drug-eluting stents include different alloys and stent designs, revisions in the polymer or drug utilized, and, ultimately, bioabsorbable platforms. [Rev Cardiovasc Med. 2007;8(suppl 1):S11-S18]
Stent Thrombosis: Role of Compliance and Nonresponsiveness to Antiplatelet Therapy Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis
Percutaneous coronary intervention with drug-eluting stents has revolutionized the management of patients with symptomatic coronary artery disease. Although this strategy significantly reduces the incidence of restenosis and repeat revascularization, concern has been raised about an increased frequency of late stent thrombosis with drug-eluting stents compared with bare-metal stents. The mechanism of stent thrombosis remains unclear, and various hypotheses have been described. Platelets are believed to play a pivotal role in the development of stent thrombosis, with pathological studies demonstrating an abundance of platelets within the occlusive thrombi. Premature discontinuation and nonadherence to antiplatelet therapy are considered important risk factors for late stent thrombosis. Early identification of vulnerable patients and definition of the role of antiplatelet nonresponsiveness in the development of stent thrombosis should be the focus of future diagnostic and therapeutic strategies. [Rev Cardiovasc Med. 2007;8(suppl 1):S19-S26]
Primary Prevention, Treatment, and Secondary Prevention of Late and Very Late Stent Thrombosis Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis
The occurrence of late and very late thrombotic complications in association with drug-eluting stents (DES) has recently garnered much attention, but these complications are also associated with bare-metal stents (BMS). Predisposing factors for BMS thrombosis, both early and late, include noncompliance with antiplatelet agents, an exercise-induced procoagulant state, brachytherapy, small stent size, underdeployment of the stent, depressed left ventricular ejection fraction, and impaired response to antiplatelet therapy. Independent predictors of DES thrombosis include premature interruption of antiplatelet therapy, primary stenting in acute myocardial infarction, total stent length, and renal failure. Prevention depends on applying an optimal stent deployment technique at the time of the index percutaneous coronary intervention (PCI), compliance with dual antiplatelet therapy, and extending antiplatelet therapy beyond current package insert recommendations. In patients who develop late stent thrombosis, efforts to achieve rapid normalization of coronary blood flow with PCI are mandatory. [Rev Cardiovasc Med. 2007;8(suppl 1):S27-S33]
New Drug-Eluting Stent Platforms to Prevent Stent Thrombosis Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis
Although earlier reports from randomized controlled clinical trials suggested that the incidence of stent thrombosis following drug-eluting stent (DES) implantation was similar to or less than that observed following bare-metal stent deployment, longerterm follow-up has revealed a persistent, protracted risk for thrombosis following DES. This apparent divergence in risk for thrombosis becomes evident beyond 6 to 12 months following deployment. The proposed etiologies of late DES thrombosis are multifactorial and differ somewhat from those factors incriminated in bare-metal stent thrombosis. Prevention strategies are in development to address polymer hypersensitivity/ inflammatory response, delayed endothelialization/vessel healing, late incomplete stent apposition, persistence of the underlying endoluminal metal prosthesis, and discontinuation of antiplatelet therapies. [Rev Cardiovasc Med. 2007;8(suppl 1):S34-S43]
Self-Assessment Post-Test Clinical Challenges in the Prevention and Treatment of Late and Very Late Stent Thrombosis