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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 6, Supplement 1, 2005

Volume 6, Supplement 1, 2005

Table of Contents

Drug-Eluting Stents: Clinical Perspectives on Drug and Design Differences
Although the introduction of coronary stents has significantly improved the treatment of patients with coronary artery disease, restenosis, due to neointimal proliferation following stent deployment and associated with a return of ischemic symptoms, has remained a critical concern. Recent studies have shown that the use of drug-eluting stents to deliver antiproliferative agents directly to the vessel wall dramatically reduces the rate of restenosis. However, important differences exist among stent designs, drugdelivery vehicles, and choices of pharmacologic agents that can significantly affect the safety and efficacy of each device. Although engineers, vascular biologists, and clinicians all agree that clinical success of drug-eluting stents requires careful integration of the individual system components, the optimal combination remains to be determined. [Rev Cardiovasc Med. 2005;6(suppl 1):S3-S12]
Use of Antiplatelet Agents and Anticoagulants for Cardiovascular Disease: Current Standards and Best Practices Critical GI Issues for the Cardiologist
Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding. [Rev Cardiovasc Med. 2005;6(suppl 4):S3-S14]
Piecing Together the Evidence on Anemia: The Link Between Chronic Kidney Disease and Cardiovascular Disease Anemia and Heart Disease
Chronic kidney disease (CKD) is now accepted as an independent cardiovascular disease (CVD)-risk state, regardless of its underlying cause. Anemia is a common feature of CKD, particularly in end-stage renal disease. Anemia is also independently associated with poorer outcomes in a wide variety of CVD states, including congestive heart failure and coronary artery disease. Anemia appears to act as an independent mortality multiplier when hemoglobin levels drop below 12 g/dL. With the independent and profound contribution of both CKD and anemia to cardiovascular mortality and morbidity, understanding the pathophysiologic links among these disease states is important. In addition, it is hoped that treatments currently under active investigation and geared specifically to attenuate the cardiovascular risk associated with anemia and CKD, such as erythropoietin therapy, will improve outcomes. This article reviews the evidence for an association among CKD, anemia, and CVD. [Rev Cardiovasc Med. 2005;6(suppl. 3):S4-S12]
Implications of Heart Failure Drug Trials: COMET, CHARM, EPHESUS
Activation of the renin-angiotensin-aldosterone and adrenergic nervous systems plays a major role in the progression of heart failure, and inhibitors and antagonists of these neurohormonal systems improve outcomes. -Blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists have been shown to improve parameters such as ventricular remodeling, ejection fraction, and renal function and to reduce rates of morbidity and mortality. This article reviews 3 recent clinical trials that have added to our knowledge of the use of these agents. Two of the studies—EPHESUS and COMET— demonstrated significant reduction in all-cause mortality, whereas the third—CHARM— showed a marginal reduction. These trials established that it is feasible to design and execute heart failure studies of sufficient scale to assess improvement in rates of mortality and morbidity. [Rev Cardiovasc Med. 2005;6(suppl 2):S4-S11]
Sudden Cardiac Death: Epidemiology and Temporal Trends
Sudden cardiac death (SCD) now accounts for more than half of all coronary heart disease deaths in the United States. The majority of cases are due to underlying coronary artery disease, and deaths from both coronary artery disease and SCD have declined markedly over the past several decades due to improved primary and secondary prevention and treatment strategies. This review examines the current statistics on the prevalence of SCD, and identifies those patients at greatest risk. It also discusses existing tests and treatments, including medication that results in neurohormonal antagonism, and devices such as the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy with a defibrillator (CRT-D). Along with increased public awareness of SCD as a major health risk, physicians are advised to implement proven effective drug and devices that can improve survival. [Rev Cardiovasc Med. 2005;6(suppl 2):S12-S20]
Pathogenesis of Anemia in Cardiorenal Disease Anemia and Heart Disease
The link between chronic heart failure (CHF) and chronic kidney disease (CKD) is well known. Approximately 50% of patients with CHF have some renal dysfunction, and 25% of patients with CKD and serum creatinine levels ranging from 1.5 mg/dL to 6 mg/dL have CHF. The association of CHF with CKD is strong and may contribute to its long-term progression. Anemia is also common in patients with CKD and contributes to increased morbidity and mortality. More recently, anemia has been found to be frequently present in patients with CHF, and its presence is associated with worse long-term CHF outcomes. Thus, anemia, CHF, and CKD may be independently related to one another, and this relationship may have important implications for their management. [Rev Cardiovasc Med. 2005;6(suppl. 3):S13-S21]
Choosing a Drug-Eluting Stent: A Comparison Between CYPHER and TAXUS
For patients with coronary artery disease undergoing percutaneous intervention, drugeluting stents (DESs) have rapidly become the standard of care. This article reviews the currently available delivery-platform/drug-carrier-vehicle combinations and those expected to become available in the future. It also evaluates and compares current DES platforms in terms of the drug involved, the delivery platform, efficacy, and safety. Currently, 2 DES platforms are available: 1 eluting sirolimus and 1 eluting paclitaxel. Sirolimus is a macrolide antibiotic with a cytostatic mechanism and an anti-inflammatory effect. Paclitaxel is a chemotherapeutic (cytotoxic) agent. The delivery platform is composed of the balloon catheter, the stent, and the drug-carrier vehicle. The carrier vehicle offers controlled drug release and enhances drug distribution. It can be a polymer that serves as a diffusion barrier or a matrix (either durable or degradable) for drug loading. Alternatively, a structural modification on the surface of the stent itself, such as a groove or well in which the drug is placed, can serve as carrier. With respect to efficacy, major trials have shown that the sirolimus platform has a lower late luminal loss rate than does the paclitaxel stent. Moreover, less intimal proliferation and obstruction occurs with the sirolimus platform than with the paclitaxel platform. Also, compared to bare metal stents, the sirolimus platform reduces late luminal loss in challenging subsets of patients. Both stents offer excellent short-term safety. To improve our understanding of these stents, a head-to-head comparison is needed. [Rev Cardiovasc Med. 2005;6(suppl 1):S13-S21]
Upper GI Risks of NSAIDs and Antiplatelet Agents: Key Issues for the Cardiologist Critical GI Issues for the Cardiologist
The use of antiplatelet/antithrombotic agents (eg, low-dose aspirin or clopidogrel) in primary or secondary intervention treatment strategies for cardiovascular disease is a common practice among cardiologists. Furthermore, these agents frequently are used concomitantly with other nonsteroidal anti-inflammatory drugs (NSAIDs) that patients are taking for a wide array of rheumatologic- or orthopedic-related complaints. These therapies, however, have defined upper gastrointestinal (UGI) risks for ulcer-related injury and complications. It is important for the cardiologist to fully understand the UGI risk profiles so that each patient is evaluated as a candidate for possible preventive co-therapy with appropriate anti-ulcer medication. [Rev Cardiovasc Med. 2005;6(suppl 4):S15-S22]
Device Trials in Heart Failure: A Focused Summary
Despite considerable progress in heart failure management with pharmacologic agents, measures to bring about significant improvements in morbidity and mortality are still needed. Cardiac resynchronization therapy (CRT) is a means to enhance myocardial function by stimulating the failing left ventricle at or near the time of right ventricular activation to synchronize ventricular depolarization. Current data from randomized, controlled trials suggest that CRT benefits patients with moderate to severe heart failure and have shown that this therapy significantly reduces mortality and hospital admissions in this group. In addition to CRT, implantable cardioverter-defibrillators have been evaluated in heart failure patients with significantly reduced left ventricular function and have been shown to reduce mortality from sudden cardiac death. This article summarizes recent device trials and discusses how best to apply their results to clinical practice. [Rev Cardiovasc Med. 2005;6(suppl 2):S21-S31]
Arterial Hemostasis, Inflammation, and Erythropoietic Growth Factors Anemia and Heart Disease
A neurohumoral link between kidneys and the heart has been established, particularly in the context of hypertension and cardiomyopathy. Beyond this neuro-endocrine pathway, another connecting system theoretically recruits growth factors that are selectively produced by the kidneys and have the ability to promote a distant reaction at the level of bone marrow. This reaction differentiates and circulates vascular progenitor cells capable of repairing the injured cardiovascular system. Reducing injuries (prevention) stabilizes disease processes by reducing tissue damage and destruction but the gradual degradation of the body’s natural repair mechanisms eventually allows progressive reactivation of disease processes. In this light, a focus on tissue repair rather than injury prevention may hold the key to controlling chronic heart diseases. This article examines the medical therapies, including recombinant human erythropoietin, that have been shown to improve the function and survival of endothelial progenitor cells and promote the healing of damaged tissue. [Rev Cardiovasc Med. 2005;6(suppl. 3):S22-S26]
Safety and Efficacy of Drug-Eluting Stents
<p>This review characterizes the relative effectiveness and safety of drug-eluting stents (DES) compared to bare metal stents. The data evaluated will include clinical and angiographic outcomes from randomized clinical trials as well as observational databases and registries including RESEARCH, e-CYPHER, and DYNAMIC, which typically include a much broader spectrum of patients. In addition, specific patient subsets, including those patients with multivessel coronary disease, will be evaluated. [Rev Cardiovasc Med. 2005;6(suppl 1):S22-S30]</p>
Strategies to Reduce the GI Risks of Antiplatelet Therapy Critical GI Issues for the Cardiologist
Low-dose aspirin and other antiplatelet agents are widely used for the management of cardiovascular disease. Due to their action on cyclooxygenase, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with upper gastrointestinal (GI) side effects, including ulcers and bleeding. Although the risk with low-dose aspirin alone is less than that with NSAIDs, given its widespread use, aspirin-related toxicity has become a substantial health care issue. Factors associated with an increased risk of aspirin-related upper GI complications are still being elucidated but most importantly include a prior history of ulcer or GI bleeding, aspirin dose, and concomitant use with an NSAID, anticoagulant, or additional antiplatelet drug. Various strategies are available to minimize the risk of developing upper GI side effects in patients taking aspirin. Gastroprotective agents that seem effective are prostaglandin analogues and proton pump inhibitors. Eradication of Helicobacter pylori also seems to reduce the risk of ulcers. Substitution by other antiplatelet agents such as clopidogrel alone does not seem to provide a safer alternative to low-dose aspirin for patients at high risk for GI side effects. [Rev Cardiovasc Med. 2005;6(suppl 4):S23-S31]
Myocardial Disease, Anemia, and Erythrocyte-Stimulating Proteins in Chronic Kidney Disease Anemia and Heart Disease
The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes. [Rev Cardiovasc Med. 2005;6(suppl. 3):S27-S34]
The Approach to Small Vessels in the Era of Drug-Eluting Stents
The treatment of small-vessel disease will occupy an increasingly important part of interventional cardiology practice and this raises several issues. The definition of “small vessels” has great implications for device size selection, and knowledge of “normal” small-vessel dimensions is important. Stents have been applied in the setting of smaller-vessel disease and future iterations of small-vessel stents will need to address several design factors. Stent strut thickness might impact on subsequent restenosis as well as late lumen loss. There has been great interest in the use of drugeluting stents for small vessels. Randomized clinical trials of sirolimus-eluting versus bare metal stents in the treatment of small-vessel disease have shown significant improvements in the rates of target lesion revascularization and restenosis with sirolimus-eluting stents. These improvements in restenosis rates are attributable to the low levels of late loss with the drug-eluting stent. [Rev Cardiovasc Med. 2005;6(suppl 1):S31-S37]
Strategies to Improve the Use of Evidence-Based Heart Failure Therapies
and mortality. Despite compelling scientific evidence that angiotensin-converting enzyme inhibitors, -blockers, and aldosterone antagonists reduce hospitalizations and mortality in HF patients, these life-prolonging therapies continue to be underutilized. Recently, device therapy for HF, including implantable cardioverter-defibrillators and cardiac resynchronization devices, has also been demonstrated to result in substantial mortality reduction. A number of studies in a variety of clinical settings have documented that a significant proportion of HF patients are not receiving treatment with these guideline-recommended, evidence-based therapies when guided by conventional care. Treatment gaps in providing other components of HF patient care, including patient education, have also been documented. The demonstration that initiation of cardiovascular protective medications before hospital discharge results in a marked increase in treatment rates, improved long-term patient compliance, and better clinical outcomes has led to the revision of national guidelines to endorse this approach as the standard of care. Recent studies demonstrated that hospital-based systems can improve medical care and education of hospitalized HF patients and accelerate use of evidencebased, guideline-recommended therapies by administering them before hospital discharge. HF disease management programs have also been shown to improve HF treatment, resulting in substantial reduction in hospitalizations and mortality. Further efforts are needed to ensure the implementation of effective strategies and systems that increase the use of evidence-based therapies in the hospital and outpatient settings to reduce the substantial HF morbidity and mortality risk. [Rev Cardiovasc Med. 2005;6(suppl 2):S32-S42]