Judy W. M. Cheng

Patient-reported adherence to guidelines of the Sixth Joint National Committee on prevention, Detection, Evaluation, and Treatment of High Blood pressure

Objectives. To compare antihypertensive drug compliance with treatment guidelines established by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), and to identify patient adherence to antihypertensive drugs and factors affecting prescribing patterns.

New Recommendations from the 1999 American College of Cardiology/American Heart Association Acute Myocardial Infarction Guidelines

OBJECTIVE: To review literature relating to significant changes in drug therapy recommendations in the 1999 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for treating patients with acute myocardial infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language clinical trials, reviews, and editorials researching the role of drug therapy and primary angioplasty for AMI that were referenced in the guidelines were included. Additional data published in 2000 or unpublished were also included if relevant to interpretation of the guidelines. STUDY SELECTION: The articles selected influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI patients. This review highlights important changes in AMI drug therapy recommendations by reviewing the results of recent clinical trials. Insights into evolving drug therapy strategies that may impact future guideline development are also described. CONCLUSIONS: Several changes in drug therapy recommendations were included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between fibrin-specific agents is unclear at this time. Low response rates to thrombolytics have been noted in the elderly, women, patients with heart failure, and those showing left bundle-branch block on the electrocardiogram. These patient groups should be targeted for improved utilization programs. The use of glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST—segment elevation MI was emphasized. Small trials combining reduced doses of thrombolytics with GP IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates without increasing bleeding risk, but firm conclusions cannot be made until the results of larger trials are known. Primary percutaneous coronary intervention (PCI) trials suggest lower mortality rates for primary PCI when compared with thrombolysis alone. However, primary PCI, including coronary angioplasty, is only available at approximately 13% of US hospitals, making thrombolysis the preferred strategy for most patients. Clopidogrel has supplanted ticlopidine as the recommended antiplatelet agent for patients with aspirin allergy or intolerance following reports of a better safety profile. The recommended dose of unfractionated heparin is lower than previously recommended, necessitating a separate nomogram for patients with acute coronary syndromes. Routine use of warfarin, either alone or in combination with aspirin, is not supported by clinical trials; however, warfarin remains a choice for antithrombotic therapy in patients intolerant to aspirin. β -Adrenergic receptor blockers continue to be recommended, and emphasis is placed on improving rates of early administration (during hospitalization), even in patients with moderate left ventricular dysfunction. New recommendations for drug treatment of post-AMI patients with low high-density lipoprotein cholesterol and/or elevated triglycerides are included, with either niacin or gemfibrozil recommended as an option. Supplementary antioxidants are not recommended for either primary or secondary prevention of AMI, with new data demonstrating lack of efficacy for vitamin E in primary prevention. Estrogen replacement therapy or hormonal replacement therapy should not be initiated solely for prevention of cardiovascular disease, but can be continued in cardiovascular patients already taking long-term therapy for other reasons. Bupropion has been added as a new treatment option for smoking cessation. As drug therapy continues to evolve in treating AMI, more frequent updates of therapy guidelines will be necessary.

L-Arginine in the Management of Cardiovascular Diseases

OBJECTIVE: To examine the role of L-arginine in the management of cardiovascular diseases. DATA SOURCES: A MEDLINE search (1966–April 2000) of review articles, using the search terms arginine, nitric oxide, and cardiovascular diseases, was conducted. After reviewing these articles, primary studies using the search terms arginine, hypercholesterolemia, hypertension, diabetes, smoking, ischemic heart disease, and heart failure were reviewed. STUDY SELECTION: English-language human studies were selected and evaluated based on quality of review. DATA SYNTHESIS: Small-scale studies have demonstrated that intravenous L-arginine augments endothelial function by enhancing vasodilation and reducing monocyte adhesion. Oral supplementation demonstrated similar effects as well as improvement of exercise ability in patients with cardiovascular diseases. CONCLUSIONS: L-arginine improves the management of multiple cardiovascular diseases. However, most published human studies are small. Before therapy can be routinely recommended, larger, well-designed studies are required to confirm its effect.

Fenoldopam in the Prevention of Contrast Media—Induced Acute Renal Failure

OBJECTIVE: To examine the role of fenoldopam in prevention of contrast media—induced acute renal failure (ARF). DATA SOURCES: A literature search of MEDLINE (from 1966 to October 2000) was performed using the following title search terms: fenoldopam, contrast, and renal failure. STUDY SELECTION: English-language human studies, abstracts, and pertinent animal data were reviewed. DATA SYNTHESIS: Small trials using animals with artificially induced ARF receiving fenoldopam demonstrated improvement in renal function. Preliminary trials in healthy humans have also demonstrated similar results using doses not affecting systemic blood pressure. CONCLUSIONS: Fenoldopam may have a role in the management of ARF induced by contrast dye. However, due to the lack of a large-scale study, it cannot be routinely recommended.

Updates on cytochrome P450-mediated cardiovascular drug interactions.

Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important role in the metabolism of steroid hormones, fatty acids, and many medications. Many agents used for management of cardiovascular diseases are substrates, inhibitors, or inducers of CYP450 enzymes. When two agents that are substrates, inhibitors, or inducers of CYP450 are administered together, drug interactions with significant clinical consequences may occur. This review discusses CYP450-mediated cardiovascular drug interactions as well as noncardiovascular drug interactions that produced significant cardiovascular side effects. The principles in predicting drug interactions are also discussed.

Infection and Atherosclerosis — Focus on Cytomegalovirus and Chlamydia Pneumoniae

BACKGROUND AND OBJECTIVE: Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (i.e, cytomegalovirus and Chlamydia pneumoniae) in atherogenesis, and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to infectious agents and coronary atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant seroepidemiologic and pathologic studies and animal models evaluating the role of cytomegalovirus or C. pneumoniae in coronary atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible role of cytomegalovirus and C. pneumoniae in the pathogenesis of atherosclerosis, as well as studies examining the use of antimicrobial and antiviral agents for reduction of cardiovascular events, are reviewed and critiqued. CONCLUSIONS: Current data do not allow us to determine whether infection is a cause or a cofactor of atherosclerosis. These uncertainties can be resolved by larger scale seroepidemiologic, pathologic, and interventional studies. Such efforts will contribute to identifying populations that are appropriate for particular surveillance or specific interventions, such as antibiotics or antiviral therapy.

Use of Erythropoietin in Heart Failure Management

OBJECTIVE To review the use of erythropoietin for anemia in heart failure (HF). DATA SOURCES Peer-reviewed articles in MEDLINE (1966–June 2004) were identified and citations from available articles were reviewed using the search terms anemia, erythropoietin, and heart failure. DATA SYNTHESIS Anemia worsens HF prognosis. Clinical studies in patients with New York Heart Association Class III/IV HF who had hemoglobin <12 mg/dL and were refractory to maximal medical management showed that erythropoietin improves symptoms. Larger scale studies with mortality endpoints are required to confirm the benefits. CONCLUSIONS In selected patients with severe, chronic HF, erythropoietin may be considered for functional improvement. However, routine use of this treatment strategy is not recommended until more data are available.

Drug Therapy Recommendations from the 2005 ACC/AHA Guidelines for Treatment of Chronic Heart Failure

Objective: To review and discuss key aspects of the drug therapy recommendations in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF) in the Adult. Data Sources: Data were obtained from the ACC/AHA 2005 Guideline Update for Chronic HF. English-language clinical trials, observational studies, and pertinent review articles evaluating the pharmacotherapy of chronic HF were identified, based on MEDLINE searches through January 2006. Study Selection: Articles presenting information that impacts the evidence base for recommendations regarding the use of various drug therapies in patients with chronic HF were evaluated. Data Synthesis: The ACC/AHA 2005 Guideline Update for HF provides revised, evidence-based recommendations for the treatment of chronic HF. The new guidelines are based on a staging system that recognizes both the development and progression of HF. Recommendations are provided for 2 stages of patients (A and B) who do not yet have clinical HF but are clearly at risk and 2 stages (C and D) that include patients with symptomatic HF. The guidelines continue to emphasize the important role of neurohormonal blockade with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated recommendations address the roles of combination therapy and the selective addition of hydralazine and isosorbide dinitrate. Along with specific drug recommendations, information on the practical use of various drugs is provided. Although the guidelines primarily focus on HF due to systolic dysfunction, general recommendations are also provided for patients with preserved systolic function. Conclusions: The ACC/AHA 2005 Guideline Update provides evidence-based recommendations for healthcare professionals involved in the care of adults with chronic HF. Recent clinical trial findings have further clarified the evolving role of neurohormonal-blocking drugs in the prevention and treatment of HF.

Early Experiences and Clinical Implications of Drug-Eluting Stents: Part 1

OBJECTIVE To review the pathogenesis of in-stent restenosis and the evolution of drug-eluting stents (DES). DATA SOURCES Using the search terms sirolimus, paclitaxel, and drug-eluting stents, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966—June 2003). Recent meeting abstracts were accessed through the American Heart Association and the American College of Cardiology Web sites. Citations from available articles were also reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION Published reviews and studies showing the effects of in-stent restenosis and drug-coated and -eluting stents were evaluated and reviewed. DATA SYNTHESIS Coronary stent implantation is a common form of percutaneous coronary interventions. Approximately 20–30% of patients undergoing stent placement develop restenosis 6 months after the procedure. The primary cause of in-stent restenosis is neointimal proliferation and subsequent accumulation of extracellular matrix, collagen, and macrophages. Eluting stents with an antimitotic agent may reduce the extent of restenosis. Research is ongoing in terms of finding the ideal combination of antimitotic agent, stent, and eluting medium to create the perfect stent. CONCLUSIONS Research over the last decade has led to a better understanding of the pathogenesis of in-stent restenosis and ways to prevent restenosis. DES are being developed as one of the strategies to prevent restenosis.

Updates on cytochrome p450-mediated cardiovascular drug interactions.

Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important role in the metabolism of steroid hormones, fatty acids, and many medications. Many agents used for management of cardiovascular diseases are substrates, inhibitors, or inducers of CYP450 enzymes. When two agents that are substrates, inhibitors, or inducers of CYP450 are administered together, drug interactions with significant clinical consequences may occur. This review discusses CYP450-mediated cardiovascular drug interactions as well as noncardiovascular drug interactions that produced significant cardiovascular side effects. The principles in predicting drug interactions are also discussed.