Download Updates in the Management of Stable Ischemic Heart Disease

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Special
Report
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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. Am J
Med Sci. 2010;339:568–72.
Morrow DA, Scirica BM, Chaitman BR, et al. Evaluation of the glycometabolic effects of
ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized
controlled trial. Circulation. 2009;119:2032–9.
Sobel BE. Coronary revascularization in patients with type 2 diabetes and results of the BARI
2D trial. Coron Artery Dis. 2010;21(3):189–98.
Simoons ML, Windecker S. Controversies in cardiovascular medicine: chronic stable
coronary artery disease: drugs vs. revascularization. Eur Heart J. 2010;31:530–41.
Newby LK, LaPointe NM, Chen AT, et al. Long-term adherence to evidence-based secondary
prevention therapies in coronary artery disease. Circulation. 2006;113:203–12.
Maron DJ, Boden WE, O’Rourke RA, et al. Intensive multifactorial intervention for stable
coronary artery disease: optimal medical therapy in the COURAGE (Clinical Outcomes
Utilizing Revascularization and Aggressive Drug Evaluation) trial. 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.
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1.
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2.
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3.
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8.