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APhA Special Report ® Supplement to Pharmacy Today A Continuing Pharmacy Education Activity • December 2010 Updates in the Management of Stable Ischemic Heart Disease Assess Your Knowledge Take a moment to assess your current knowledge by answering the following questions. After reading the monograph, you’ll see these questions again as part of the CPE exam. Angina is a significant health issue in the United States, affecting: a. 4.7 million people. b. 5.5 million people. c. 10.2 million people. d. More men than women. A recently understood factor involved in the pathophysiology of angina is: a. Underlying atherosclerosis. b. Concurrent diabetes. c. Changes in sodium-calcium regulation in myocytes. d. An imbalance between O2 supply and demand. Pharmacists should advise their patients with stable ischemic heart disease: a. To have a friend or family member drive them to the hospital if their symptoms intensify. b. To avoid large meals and rich foods that trigger anginal pain. c. That men require higher doses of antianginal medications than women. d. To take nitroglycerin only after an attack of anginal pain begins. Introduction: Stable IHD Angina pectoris is a distressing symptom of ischemic heart disease (IHD). The American Heart Association (AHA) estimates that 10.2 million Americans over the age of 20 years suffer from angina (based on 2006 data); among them, 4.7 million are men and 5.5 million are women. AHA also estimates that 500,000 new cases of stable angina occur each year in Americans aged 45 years and older, with more new cases among men (320,000) than women (180,000).1 Although angina is more prevalent among women, the risk of cardiovascular (CV) events is higher among men.2 Stable angina is characterized by an uncomfortable sensation in the chest, jaw, neck, shoulders, back, or arm. Patients describe the chest discomfort as a sensation of pressure, heaviness, tightness, squeezing, burning, or choking. Some patients—particularly women, elderly adults, and people with coexisting diabetes—may have atypical symptoms such as sharp stabbing pain, back pain, or palpitations.3,4 Other atypical symptoms include heartburn, indigestion, weakness or dizziness, shortness of breath, or unusual fatigue.5 Episodes of chronic stable angina are usually predictable and are brought on by physical exertion. Anginal symptoms also may be triggered by emotional stress, exposure to very hot or cold temperatures, heavy meals, and smoking. This type of angina usually lasts a short time (≤5 minutes) and is quickly relieved by rest and/or sublingual nitroglycerin. It differs from unstable angina, which is an acute condition that is part of the acute coronary syndrome. Unstable angina results in persistent symptoms, often at rest, and indicates that a myocardial infarction (MI) may be imminent.2,6,7 The pain of angina is due to an imbalance in oxygen (O2) demand and supply. In patients with coronary artery disease (CAD), narrowed coronary arteries restrict the flow of oxygen-rich blood to the myocardium.8 Thus, angina is a symptom of an underlying heart problem—typically myocardial ischemia from CAD.6 (Stable angina also may be caused by cocaine or methamphetamine abuse.) Management of stable IHD is individualized for each patient, according to the cause and existence of underlying or concomitant conditions. According to Braunwald’s Heart Disease, the five aspects of medical management of stable IHD are9: 1. Identify and treat associated disease that can precipitate or worsen angina. 2. Reduce coronary risk factors (e.g., hypertension, dyslipidemia, cigarette smoking, inflammation). 3. Apply general and nonpharmacological management, with emphasis on lifestyle changes. 4. Provide appropriate pharmacological management. 5. Consider revascularization when necessary to meet the goals of therapy. CV disease has a significant impact on the health care system in the United States. The estimated combined direct and indirect cost of CAD (which affects approximately 17.6 million Americans older than 20 years of age) for 2010 is $177.7 billion.1 An analysis of national average Medicare reimbursement rates in 2000 determined that when chronic angina was positioned as the first-listed diagnosis on medical records, total direct medical costs were $1.9 billion; when listed in any position, costs were $8.9 billion.10 PROVIDER: American Pharmacists Association TARGET AUDIENCE: Pharmacists RELEASE DATE: December 1, 2010 EXPIRATION DATE: December 1, 2013 Activity Preview Angina pectoris is the symptomatic manifestation of ischemic heart disease (IHD). Recent insights into the pathophysiology of stable IHD have significantly impacted its management. Researchers are developing new therapeutic agents that address the mechanisms of this disease, specifically the role of the cardiac sodium channel. Pharmacists who are aware of current thinking about the management of stable IHD can most effectively counsel their patients who have this disorder. This monograph presents the latest information on the pathophysiology of stable IHD, therapeutic options, and its clinical impact and costs. ACPE NUMBER: 202-000-10-263-H04-P CPE CREDIT: 1 hour (0.1 CEU) ACPE ACTIVITY TYPE: Knowledge-based LEARNING LEVEL: 2 FEE: There is no fee associated with this activity. To obtain 1 hour of CPE credit (0.1 CEU) for this activity, complete the CPE exam and submit it online at www.pharmacist.com/education. A Statement of Credit will be awarded for a passing grade of 70% or better. You will have two opportunities to successfully complete the CPE exam. Pharmacists who successfully complete this activity before December 1, 2013, can receive credit. Your Statement of Credit will be available online immediately upon successful completion of the CPE exam. Development This home-study CPE activity was developed by the American Pharmacists Association. Learning Objectives At the completion of this activity, the pharmacist will be able to: Discuss the economic and clinical impact of stable ischemic heart disease and current treatment options, including drug therapy and revascularization. y Summarize the diagnosis, risk factors, and comorbid conditions in patients with stable ischemic heart disease. y Identify recent articles in the medical literature and other updates that provide insight into the treatment of stable ischemic heart disease. y State key discussion points to use in daily practice when speaking with a patient regarding stable ischemic heart disease. y Support This activity is supported by an independent educational grant from Gilead Sciences, Inc. Advisory Board Robert J. DiDomenico, PharmD Clinical Associate Professor, Pharmacy Practice University of Illinois at Chicago College of Pharmacy Chicago, Illinois Disclosures Robert J. DiDomenico, PharmD, declares that he has received honoraria as an advisory board member for Merck and Co., and as a speaker for STRIVE ACS Critical Pathways Workshop sponsored by Bristol-Myers Squibb and sanofiaventis. He also served as an investigator and received research support from Johnson & Johnson Pharmaceutical Research and Development, LLC. Mark A. Munger, PharmD, FCCP, FACC Professor, Pharmacotherapy and Internal Medicine Associate Dean, Academic Affairs University of Utah College of Pharmacy Salt Lake City, Utah Mark A. Munger, PharmD, FCCP, FACC, declares no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. Accreditation Information The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 202-000-10-263-H04-P. Pathophysiology Stable IHD occurs when an increase in O2 demand is coupled with a decrease in O2 supply. When CAD is present, blood flow through the narrowed epicardial arteries is limited as the demand for flow is increased. Usually, angina occurs when plaque obstructs at least 70% of the arterial lumen. Atherosclerosis also can cause vasomotor dysfunction, leading to inappropriate vasoconstriction and further reduction of the blood supply to the myocardium.5 The complexity of this imbalance is shown in TABLE 1. Research in recent years has uncovered cellular abnormalities that occur during myocardial ischemia. Changes in the sodiumcalcium regulation in myocytes that occur in myocardial ischemia 2 APhA’s editorial staff declares no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. This publication was prepared by Gail Dearing on behalf of the American Pharmacists Association. lead to intracellular calcium overload. This increase, in turn, leads to changes in myocardial relaxation, decreased perfusion to the myocardium, and increased O2 demand, thereby perpetuating the underlying ischemia.5 Diagnosis Evaluation of a patient presenting with symptoms suggestive of stable IHD starts with a clinical evaluation, including a careful history.5 The severity of pain varies greatly from patient to patient and is not reflective of the severity of the underlying CAD. Most clinicians use the Canadian Cardiovascular Society classification system when defining severity (see CLASSIFICATION OF STABLE ANGINA).9,12 © 2010 American Pharmacists Association. All rights reserved. Printed in the U.S.A. Table 1. Factors Contributing to the Imbalance of Myocardial O2 Demand and Supply Table 2. Risk Factors for Angina • Gender (increased risk for men and postmenopausal women) Demand • Heart rate Supply • Coronary stenosis • Hypertension • Blood pressure • Nonstenotic lesions • Cigarette smoking • Stroke volume • Platelet aggregation • Insulin resistance or diabetes • Contractility • Intraplaque hemorrhage • Excess weight or obesity • LV pressure • Vasomotion • Metabolic syndrome • LV volume • Coronary spasm • Unhealthy diet • Wall thickness • Collateral circulation • Hypercholesterolemia • Lack of physical activity • Microcirculation • Age (risk increases in men after 45 years of age, in women after 55 years of age) • Endothelial function • Family history of early heart disease • Diastolic filling time (heart rate) • O2 content, diffusion LV = left ventricular; O2 = oxygen. Source: Adapted from reference 11. Source: Reference 7. The patient’s prognosis depends on the extent of CAD and the presence of LV dysfunction and other comorbidities.5 Impact on Quality of Life Class II: Ordinary activity is slightly limited. Angina occurs when walking uphill or after meals, in cold weather, with emotional stress, or only during the first few hours after awaking. A major consequence of stable IHD is its effect on quality of life (QoL), when patients must limit their everyday tasks in an effort to prevent anginal attacks. The pain—and anticipation of pain— frequently prevent patients from pursuing hobbies and other activities that were once an enjoyable part of their lives. QoL diminishes with increasing severity of angina.5,9 Class III: Ordinary activity is markedly limited. Walking one or two blocks on a level grade or climbing one flight of stairs precipitates angina. Advances in the Management of Stable IHD Classification of Stable Angina Class I: Angina occurs with strenuous, rapid, or prolonged exertion— not with ordinary activity. Class IV: Cannot carry out any physical activity without discomfort, or angina at rest. Source: Reference 12. Reprinted with permission from the Canadian Cardiovascular Society. Laboratory tests (e.g., lipids, complete blood cell count, blood glucose, C-reactive protein) may be done to investigate the potential causes of ischemia and the presence of risk factors.5 To evaluate the presence and severity of ischemia, cardiac testing such as electrocardiography (ECG), stress testing, exercise or pharmacological myocardial perfusion imaging, coronary angiography, and multislice computed tomography scans may be ordered, although some experts advise that noninvasive stress testing should be done only if the information it provides will change the patient’s management.5,9 Risk Factors and Prognosis As a symptom of CAD, stable angina shares the same risk factors (TABLE 2). It is critical that these risk factors and conditions, if present, be addressed aggressively. The presence of stable IHD puts patients at risk for significant complications of CAD: MI, heart failure, stroke, and death.5 It is worth noting, however, that only 18% of heart attacks are preceded by longstanding angina.1 The annual mortality rate in patients with stable IHD is 3%.2,9 The risk of serious CV events is higher among men, particularly in those with diabetes, heart failure, or hypertension; in the presence of multivessel CAD; and in those with left ventricular (LV) dysfunction (i.e., ejection fraction ≤35%).2 Updates in the Management of Stable Ischemic Heart Disease All clinicians treating stable IHD must not only understand its treatment goals but also the use of evidence-based medicine to determine optimal management for specific patients. Revisions of the major professional guidelines in all areas of medicine lag behind the latest developments in any given field. In the case of stable IHD, the 2002 Guidelines for the Management of Patients With Chronic Stable Angina from AHA and the American College of Cardiology (ACC) were updated in 2007, and a major revision is anticipated at the end of 2010. It is expected that the revised recommendations will reflect the findings of recent clinical trials on pharmacological agents and revascularization procedures. The first treatment goal for patients with stable IHD is to reduce the pain and discomfort of angina, decrease the frequency of anginal episodes, and improve QoL. However, because these patients are at risk for significant complications of CAD, the second treatment goal is to prevent disease progression and reduce the risk of complications and death.5,7,9 TABLE 3 describes the goals in risk factor management. Because depression has been associated with CAD, evaluation for depression and referral or treatment as indicated are important components of the overall management of patients with stable IHD.9 Keep Up-to-Date New guidelines for managing stable IHD are due at the end of 2010. Visit the website of the Journal of the American College of Cardiology to check availability of the new guidelines: http://content.onlinejacc. org. Clinical guidelines are listed in the left column on the home page. 3 Table 3. Risk Factor Management Goals in Stable Ischemic Heart Disease Risk Factor Hypertension LDL cholesterol Non-HDL cholesterol (total cholesterol minus HDL cholesterol) Diabetes Management Goal • BP <140/90 mm Hg • With diabetes or kidney disease, BP <130/80 mm Hg • ≤100 mg/dL; attempt to reduce to <70 mg/dL • Consider high-dose statins • If triglyceride levels are 200–499 mg/ dL, reduce non-HDL cholesterol to <130 mg/dL • Consider niacin or fibrate therapy for long-term use • Achieve normal or near-normal hemoglobin A1C level of <7% • Use lifestyle changes and medications BP = blood pressure; HDL = high-density lipoprotein; LDL = low-density lipoprotein. Source: Reference 6. Changes in Lifestyle Initial treatment for patients with stable IHD involves a series of lifestyle changes to reduce risks—the same approach that is recommended for patients with CAD.6 Lifestyle modifications for secondary prevention of complications are listed in TABLE 4. Table 4. Lifestyle Modifications for Patients With Stable Ischemic Heart Disease • Achieve and maintain body mass index between 18.5 and 24.9. • Reduce or maintain weight through a balanced combination of physical activity, reduced calorie intake, and, when indicated, formal behavioral modification programs. • Engage in physical activity for 30 to 60 minutes 7 days/week (minimum 5 days/week). Include moderate-intensity aerobic activities such as brisk walking supplemented by an increase in daily activities such as taking walking breaks during the day, gardening, or housework. • Moderate alcohol consumption. • Limit sodium intake. • Maintain a diet high in whole grains, fresh fruits, vegetables, and low-fat dairy products. • Reduce intake of saturated fats to <7% of total calories and cholesterol to <200 mg/day. Limit intake of trans fat. • Stop smoking; consider use of smoking cessation programs and medications/nicotine replacement products. Try to avoid secondhand smoke. Source: References 6 and 7. Pharmacotherapy Drug therapy is one of the mainstays of treatment for patients with stable IHD to meet both the primary and secondary treatment goals. For immediate relief from anginal episodes, nitroglycerin is the drug of choice. In addition, β-blockers, calcium channel blockers (CCBs), long-acting nitrate therapy, and/or ranolazine may be prescribed for chronic use to relieve anginal symptoms and reduce episodes of angina.5,13 To address the second goal, cardioprotective medications such as antiplatelet agents, angiotensin-converting enzyme (ACE) 4 inhibitors, angiotensin II receptor blockers (ARBs), and statins are used to prevent disease progression and the occurrence of MI or death.5 For patients whose blood pressure (BP) remains elevated after antianginal therapy has been optimized, ACE inhibitors may be preferred because of their potential to reduce death and MI as well as BP. Earlier recommended treatments such as vitamin E and folic acid with or without B vitamins have not been shown to reduce CV events.5 An overview of current recommendations for pharmacotherapy in patients with stable IHD appears in TABLE 5. Table 5. Current Recommendations for Pharmacotherapy in Stable Ischemic Heart Disease Relieve or Reduce Anginal Episodes Nitrates, nitroglycerin β-Blockers Calcium channel blockers Ranolazine Source: References 5, 6, and 9. Prevent Cardiovascular Events, Death Aspirin or clopidogrel Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Statins Antianginal/Anti-ischemic Agents Nitrates act as vasodilators, reducing the heart’s workload and O2 consumption. Nitroglycerin, available as sublingual tablets or spray, is the drug of choice for acute episodes of angina. Doses of 0.3 mg to 0.6 mg usually relieve the discomfort. Nitrates also may be used long term to reduce or eliminate angina in patients with frequent anginal attacks.5,9 Because tolerance to nitrates can develop rapidly—in only 24 hours—they are dosed with a daily 10- to 14hour period without nitrates. Thus, nitrates are not recommended as monotherapy for stable IHD because patients would not be protected around the clock.5 Medications prescribed for erectile dysfunction must not be used in patients taking nitrates because of the risk of severe hypotension.14 β-Blockers are a cornerstone of angina therapy. With antiischemic, antihypertensive, and antiarrhythmic properties, they have been shown to reduce the frequency of anginal episodes. By slowing heart rate, β-blockers reduce myocardial O2 requirements. β-Blockers also reduce exercise-induced increases in BP and limit increases in contractility associated with exercise.5,9 CCBs inhibit the movement of calcium ions through slow channels in cardiac and smooth muscle membranes, reducing myocardial O2 demand and inducing increased O2 supply.9 CCBs may be used as first-line therapy in patients with a contraindication or intolerance to β-blockers.13 Ranolazine is a novel agent that is indicated as first-line therapy for chronic angina. The newest antianginal medication available in the United States, it may be used alone or in combination with β-blockers, nitrates, CCBs, antiplatelet therapy, statins, ACE inhibitors, and ARBs.15 In randomized clinical trials, ranolazine reduced the symptoms of chronic stable angina, improved exercise capacity, and delayed the onset of angina symptoms or ECG signs of ischemia during exercise.15,16 Ranolazine is thought to work by inhibiting the late sodium current in cardiac myocytes, thereby reducing the sodium and calcium overload that follows ischemia. This reduction improves myocardial relaxation and reduces LV diastolic stiffness, which in turn enhances myocardial contractility and perfusion.9,17,18 American Pharmacists Association Ranolazine differs from the other three drug classes by preventing the cellular consequences of ischemia (e.g., calcium overload from disrupted sodium-calcium regulation) rather than by reducing O2 demand (e.g., decreased BP, heart rate, contractility) as the other drugs do. Hence, when bradycardia, heart rate, or hypotension are a concern, ranolazine offers an alternative treatment, because its anti-ischemic effects are usually achieved without clinically meaningful changes in BP or heart rate.5,9,17 Additional information on this agent can be found in the 2009 APhA New Therapeutics Bulletin: Ranexa (ranolazine) available at www.pharmacist.com/ AM/Template.cfm?Section=Home2&TEMPLATE=/CM/ContentDisplay. cfm&CONTENTID=20061. Cardioprotective Agents Antiplatelet therapy is considered the standard of care in patients with CAD because it has been shown to prevent coronary thrombosis and reduce CV events such as MI and death.5 Patients should take low-dose aspirin (81–162 mg/day) indefinitely; if they cannot tolerate aspirin, clopidogrel is recommended.6 ACE inhibitors are recommended for patients with stable IHD who have concurrent hypertension, diabetes, or chronic kidney disease unless contraindicated owing to other health factors. ACE inhibitors have demonstrated efficacy in reducing ischemic endpoints.19 Patients with reduced ejection fraction, especially if <40%, also should be considered for ACE inhibitor therapy.5,6 ARBs are used in many patients with stable IHD, particularly those who are intolerant of ACE inhibitors and who have hypertension or heart failure. ARBs also are administered to patients who have had a heart attack and whose ejection fraction is <40%.6 Combined treatment with an ACE inhibitor and an ARB is an area of controversy. While some believe that the combination does not show any benefit over an ACE inhibitor alone, others have determined that the combination may be beneficial.20 (See ARE YOU UP-TO-DATE ON ACE INHIBITORS AND ARBS?) Taking the combination can cause more serious adverse effects than either drug alone, including syncope, hypotension, or elevated creatinine.19,20 Are You Up-to-Date on ACE Inhibitors and ARBs? In 2010, the Agency for Healthcare Research and Quality released the findings of its systematic review of randomized clinical trials on the efficacy of ACE inhibitors and ARBs. The report concludes that adding an ACE inhibitor to standard treatment (i.e., aspirin, β-blockers, and aggressive modification of risk factors) in patients with stable IHD preserved LV function and can improve outcomes in these patients; specifically, ACE inhibitors reduced the risk for mortality, stroke, and MI. ARBs also were found to reduce the composite of these endpoints. The report notes that combining ACE inhibitors and ARBs appears to increase harm in some patients—increasing risks for hypotension and syncope. The report is available at www.effectivehealthcare.ahrq.gov. Source: Reference 19. Statins are widely recognized for their benefits in reducing lowdensity lipoprotein cholesterol in patients with hyperlipidemia. They also have been shown to reduce the progression of atherosclerosis and the risk of MI and death in patients with stable IHD who have normal lipid levels.2,3 Updates in the Management of Stable Ischemic Heart Disease Safety Considerations The safety of traditional agents used for the treatment of stable IHD is well known. Ranolazine has been deemed safe and well tolerated in patients with stable IHD including those with diabetes, heart failure, and renal impairment, as well as geriatric patients.15 The adverse effects of commonly used medications in stable IHD are summarized in TABLE 6. Table 6. Overview of Adverse Effects Associated With Antianginal and Cardioprotective Agents Drug Class Antianginal Agents β-Blockers Calcium channel blockers Long-acting nitrates Ranolazine Adverse Effects • Bradycardia, hypotension, fatigue, and sexual dysfunction. • Contraindicated in patients with existing bradycardia, hypotension, second- or third-degree atrioventricular block, and severe asthma. • Dihydropyridine agents: reflex tachycardia, peripheral edema, headache, dizziness, flushing, and hypotension. • Non-dihydropyridine agents: bradycardia, hypotension, dizziness, flushing, edema, and atrioventricular block. • Hypotension, dizziness, and headache. • Concomitant use of agents for erectile dysfunction is contraindicated because of the risk of profound hypotension. • Dizziness, headache, constipation, and nausea. • Minor prolongation of QT interval may occur. Cardioprotective Agents Angiotensinconverting enzyme inhibitors Angiotensin II receptor blockers Antiplatelet agents • Cough, orthostatic hypotension, hyperkalemia, angioedema, and serious birth defects. • Hyperkalemia, angioedema, orthostatic hypotension, and birth defects. • Low-dose aspirin: gastrointestinal bleeding. • Clopidogrel: headache, abdominal pain, flu-like symptoms, and minor bleeding/ purpura. Statins • Headache, constipation, diarrhea, myalgia, and nausea. Source: References 2, 3, 5, 14, 15, 19, and 21. Revascularization Revascularization therapies are an important component of the treatment strategy for patients with stable IHD. Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery may be employed in addition to medical therapy when necessary to meet the goals of therapy. However, questions have been raised regarding the benefits of revascularization over optimal medical therapy. Recent trials such as the landmark Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) and Clinical Outcomes Utilizing Revascularization and Aggressive 5 Drug Evaluation (COURAGE) studies showed that coronary artery revascularization on top of optimal medical treatment did not improve patients’ long-term prognosis.11,22,23 Revascularization is appropriate when medical therapy is ineffective, according to the 2009 Appropriateness Criteria for Coronary Revascularization from AHA/ACC and a group of key CV specialty societies. CABG or PCI procedures are necessary in multivessel CAD or in two-vessel disease when the proximal portion of the left anterior descending artery is involved. For other patients, decisions should be based on the extent of myocardial ischemia, the intensity of ischemic symptoms, the extent of medical therapy received, and the findings of noninvasive diagnostic techniques.23,24 Patients should understand that revascularization procedures will not cure their disease and that pharmacologic agents should be continued.5 Patient Considerations in Therapy Selection Gender Continuous ECG monitoring has shown that women have more documented ischemic episodes than men. Women with ischemia are more likely to report variable pain thresholds, palpitations, or sharp stabbing pain. They have more symptomatic episodes of stable angina than men and achieve less relief of symptoms with current therapy.4 Although women have a 20% higher prevalence of stable IHD than men, they are at lower risk of serious CV events such as MI and death. Notably, women are more likely to be misdiagnosed and under-treated for both angina and secondary prevention.2,4 Diabetes Nearly 3 million Americans have coexisting diabetes mellitus and CAD. The presence of both conditions increases the risk of MI and death in patients with established CAD.5 Antianginal drug therapy must be individualized in patients with stable IHD and diabetes. For example, patients with diabetes who have had an MI and who have heart failure or require additional BP control would likely benefit significantly from an ACE inhibitor.5 A reduction in hemoglobin A1C in diabetes patients receiving ranolazine for acute coronary syndrome was observed in a secondary post hoc analysis.25 Further study is needed to determine the clinical significance. The use of revascularization procedures in patients with stable IHD and diabetes requires specialized strategies. Patients with diabetes who undergo revascularization experience more adverse CV events than patients without diabetes.26 The BARI 2D trial investigated the safety and efficacy of revascularization in patients with type 2 diabetes and stable chronic coronary disease. The researchers reported that survival after CABG or PCI was comparable with survival in patients receiving optimal medical therapy alone. The BARI 2D investigators concluded that evaluation for revascularization can be deferred until signs and symptoms worsen, except in patients with severe angina or multivessel CAD.26 Heart Failure Chronic CAD is the most common cause of systolic heart failure.27 Patients with stable IHD and heart failure may experience cardiac dilation, mitral regurgitation, or tachyarrhythmias. These 6 effects can increase myocardial O2 demand, thereby increasing the frequency and severity of angina.9 Some drugs used for stable IHD (i.e., β-blockers and ARBs) also are used for heart failure; ranolazine is being studied in patients with heart failure. Implications for Pharmacists Pharmacists can help ensure optimal outcomes for their patients with stable IHD through communication and education. As with all prescription medications, the pharmacist should check for drugdrug interactions; this safeguard is especially critical because some antianginal and cardioprotective medications are contraindicated for use with other medications that these patients may be taking. The pharmacist also has a responsibility to educate patients about each of their medications and to make sure patients know how to store them and when to replace them.7 Pharmacists also should instruct their patients to self-monitor treatment by keeping track of measures such as BP, blood glucose, number of angina episodes, and their use of sublingual nitroglycerin. Because women with stable IHD are often under-treated, the pharmacist can help to improve outcomes by ensuring that these patients are receiving appropriate medications at the proper doses. It has been suggested that physicians prescribe lower doses of antianginal/anti-ischemic medications than what was proven effective in clinical trials. Higher doses and combined therapy are not used in patients, particularly women, who could be free of angina if treated more appropriately.2 Many patients with stable IHD will qualify for medication therapy management (MTM) because they have multiple chronic conditions and are likely taking multiple medications. Through MTM, pharmacists can make sure their patients are receiving the most appropriate therapy for their angina in a number of ways, including working with patients to identify medication-related problems such as drug interactions, adverse effects, adherence issues, and evaluating for effectiveness. More information about MTM is available by going to APhA’s website www.pharmacist.com and clicking on “MTM Central.” When counseling patients, pharmacists should emphasize the importance of taking all medications as prescribed. Unfortunately, a 2006 U.S. study found less than ideal adherence to aspirin (71%), β-blockers (46%), and lipid-lowering therapy (44%).28 Among patients taking a combination of aspirin, β-blockers, and lipidlowering therapy, adherence was only 21%.29 Pharmacists can advise patients to avoid angina triggers (e.g., slow down if physical exertion precipitates angina, avoid large meals and rich foods that trigger angina) and try to avoid situations that cause emotional stress.7 Additionally, pharmacists can recommend that patients take a dose of sublingual nitroglycerin before undertaking physical activities that have triggered symptoms in the past; doing so will prevent anginal pain for up to 40 minutes.9 Patients should be educated to understand the pattern of their angina. If the pattern changes (i.e., if it occurs more often, lasts longer, is more severe, occurs without exertion, or does not go away with rest or medication), they should seek medical help promptly.7 Educate patients and their families to know how and when to seek medical attention and advise them to develop an emergency plan. Emphasize that the fastest way to get lifesaving treatment is to call 911; American Pharmacists Association emergency medical services personnel can begin treatment when they arrive, up to an hour sooner than if a patient is driven to the hospital. Furthermore, people are likely to receive faster attention in the hospital if they arrive by ambulance.8 Finally, individuals with chronic conditions such as stable IHD are particularly vulnerable to complications of influenza, which causes more than 36,000 deaths and 225,000 hospitalizations every year in the United States. Patients with stable IHD should get an annual flu shot, as recommended in the 2007 guideline update.6 5. 6. 7. 8. 9. Are You Up-to-Date on the Latest Information? 10. For information from the latest published papers—both reports on clinical trials and therapeutic reviews—consult these articles in the medical literature: 11. 12. 13. • COURAGE trial: References 24 and 29 • BARI 2D trial: Reference 26 14. • Ranolazine Open Label Experience (ROLE) trial: Reference 16 • Guidelines for stable IHD/angina: – ACC/AHA 2002: Reference 30 – ACC/AHA 2007 Update: Reference 6 • Management of stable IHD: References 2, 4, 5, 11, 14, 17, 22, and 27 Summary Angina affects more than 10 million Americans. Overall treatment of stable IHD aims to reduce symptoms and improve prognosis. Treatment options include lifestyle changes and medication to modify risk factors, reduce symptoms, and prevent MI and death. Treatment decisions in patients with stable IHD should be based on determining the extent of ischemia, severity of angina, and use of medical therapies alone or in combination with revascularization procedures. Furthermore, special consideration should be given to LV function, coronary anatomy, women, older adults, and patients with concomitant diabetes or heart failure in determining the appropriate course of action. Clinicians today have more potent tools to treat stable IHD than ever before. Evidence-based decisions about current therapies enable patients to live pain-free, participate in physical and social activities, and enjoy a fuller, longer life.14 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. References 1. 2. 3. 4. American Heart Association. Heart disease and stroke statistics—2010 update. Circulation. 2010;121:e46–e215. Available at: http://circ.ahajournals.org/cgi/content/full/121/7/e46. Accessed August 16, 2010. O’Rourke RA. Alternative strategies for the management of chronic stable angina. Curr Probl Cardiol. 2010;35:384–446. Abrams JA. Chronic stable angina. N Engl J Med. 2005;352:2524–33. Kones R. Recent advances in the management of chronic stable angina I: approach to the patient, diagnosis, pathophysiology, risk stratification, and gender disparities. Vasc Health Risk Manag. 2010;6:635–56. Updates in the Management of Stable Ischemic Heart Disease 28. 29. 30. Trujillo TC, Dobesh PP. Traditional management of chronic stable angina. Pharmacotherapy. 2007;27:1677–92. Fraker TD, Fihn SD, Gibbons RJ, et al. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina. Circulation. 2007;116:2762–72. National Heart Lung and Blood Institute. Diseases and Conditions: Angina. Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Angina/Angina_All.html. Accessed September 3, 2010. American Heart Association. Know the Facts, Get the Stats 2007. Available at: http://www. americanheart.org/downloadable/heart/116861545709855-1041%20KnowTheFactsStats07_ loRes.pdf. Accessed August 16, 2010. Libby P, Bonow R, Mann DL, et al., eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008. Javitz HS, Ward MM, Watson JB, et al. Cost of illness of chronic angina. Am J Manag Care. 2004;10(11 suppl):S358–69. Orsini E, Zito GB. Matching pathophysiology and evidence-based medicine for optimal management of ischemic heart disease. J Cardiovasc Med. 2010;11:469–79. Campeau L. Letter: grading of angina pectoris. Circulation. 1976;54:522–3. Battisti A, Tizzani E. Current treatment status of stable angina: medical treatment versus percutaneous coronary intervention versus coronary artery by-pass grafting. J Indian Med Assoc. 2009;107:685–6, 691–4. Kones R. Recent advances in the management of chronic stable angina II: anti-ischemic therapy, options for refractory angina, risk factor reduction, and revascularization. Vasc Health Risk Manag. 2010;6:749–74. Ranexa [package insert]. Palo Alto, CA: Gilead Sciences, Inc.; March 2009. Reffelmann T, Kloner RA. Ranolazine: an anti-anginal drug with further therapeutic potential. Expert Rev Cardiovasc Ther. 2010;8:319–29. Aslam S, Gray D. Ranolazine (Ranexa) in the treatment of chronic stable angina. Adv Ther. 2010;27(4):193–201. Maier LS. A novel mechanism for the treatment of angina, arrhythmias, and diastolic dysfunction: inhibition of late I(Na) using ranolazine [abstract]. J Cardiovasc Pharmacol. 2009;54(4):279. Agency for Healthcare Research and Quality. Effective Health Care Program: Comparative Effectiveness of Angiotensin Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Stable Ischemic Heart Disease. October 2009. Available at: http://www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed August 17, 2010. Chaitman BR, Hartigan PM, Booth DC, et al. Do major cardiovascular outcomes in patients with stable ischemic heart disease in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial differ by healthcare system? Circ Cardiovasc Qual Outcomes. 2010;3:476–83. Berger PB, Bhatt DL, Fuster V, et al.; CHARISMA Investigators. Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease. Circulation. 2010;121:2575–83. Pfisterer ME, Zellweger MJ, Gersh BJ. Management of stable coronary artery disease. Lancet. 2010;375(9716):763–72. Patel MR, Dehmer GJ, Hirshfeld JW, et al. ACCF/SCAI/STS/AATS/AHA/ASNC 2009 appropriateness criteria for coronary revascularization. Circulation. 2009;119:1130–52. Toutouzas K, Synetos A. Percutaneous coronary intervention in chronic stable angina. 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J Am Coll Cardiol. 2010;55:1348–58. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina. Circulation. 2003;107:149–58. 7 APhA Special Report ® CPE Exam Instructions: The assessment questions printed below allow you to preview the online CPE exam. Please review all of your answers to be sure you have marked the proper letter on the online CPE exam. There is only one correct answer to each question. 1. Angina is a significant health issue in the United States, affecting: a. 4.7 million people. b. 5.5 million people. c. 10.2 million people. d. More men than women. 2. A symptom typical of stable angina is: a. Dizziness. b. Squeezing chest discomfort. c. Sharp, shooting pain. d. Back pain. Which of the following characteristics is not associated with stable IHD? a. Chest discomfort. b. Occurs primarily at rest. c. Triggered by emotional stress. d. Quickly relieved by sublingual nitroglycerin or rest. 4. A recently understood factor involved in the pathophysiology of angina is: a. Underlying atherosclerosis. b. Concurrent diabetes. c. Changes in sodium-calcium regulation in myocytes. d. An imbalance between O2 supply and demand. 5. Recommendations for managing risk factors in patients with stable IHD include reducing: a. BP to 120/80 mm Hg. b. LDL cholesterol to ≤100 mg/dL. c. A1C to 8%. d. Triglyceride levels to <200 mg/dL. 6. Drug therapy to relieve symptoms and reduce episodes of angina includes: a. Clopidogrel. b. ACE inhibitors. c. ARBs. d. β-Blockers. 7. To reduce CV endpoints such as MI and death, physicians may prescribe: a. Ranolazine. b. Folic acid with B vitamins. c. β-Blockers. d. ACE inhibitors. The Agency for Healthcare Research and Quality has recently reported that: a. ACE inhibitors can improve anginal symptoms in patients with stable IHD. b. ARBs can reduce individual risk factors such as hypertension and hyperlipidemia. c. Combining ACE inhibitors and ARBs can increase risks for MI. d. Adding ACE inhibitors to standard therapy in patients with preserved LV function reduces the risk of death, MI, and stroke. 9. Ranolazine is unique among antianginal medications in that it: a. Is indicated for first-line therapy in stable IHD. b. Can be used with β-blockers and nitrates. c. Reduces the symptoms of stable angina. d. Achieves anti-ischemic effects without significant changes in BP or heart rate. 10. Which clinical trial concluded that revascularization in patients with stable chronic coronary disease and diabetes can be deferred until symptoms worsen? a. COURAGE. b. BARI 2D. c. MERLIN-TIMI 36. d. ROLE. 11. The risk of MI and death is increased in patients with stable IHD who: a. Have CAD and diabetes. b. Undergo PCI or CABG. c. Have an ejection fraction of 40%. d. Are women. 12. Pharmacists should advise their patients with stable IHD: a. To have a friend or family member drive them to the hospital if their symptoms intensify. b. To avoid large meals and rich foods that trigger anginal pain. c. That men require higher doses of antianginal medications than women. d. To take nitroglycerin only after an attack of anginal pain begins. CPE Instructions Completing a posttest at www.pharmacist.com/education is as easy as 1-2-3… 1. Go to Online CPE Quick List and click on the title of this activity. 2. Log in. APhA members enter your user name and password. Not an APhA member? Just click “Create one now” to open an account. No fee is required to register. 3. Successfully complete the CPE exam and evaluation form to gain immediate access to your Statement of Credit. Live step-by-step assistance is available Monday through Friday, 8:30 AM to 5:00 PM ET from APhA Member Services at 800-237-APhA (2742) or e-mail [email protected]. American Pharmacists Association • 2215 Constitution Avenue, NW • Washington, DC 20037 • 800-237-APhA • Pharmacist.com 10-455 3. 8.