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					                                 Pharmacotherapy of Coronary Artery Disease
                                            Molly Roberts, PharmD Candidate 2007

Epidemiology Coronary artery disease is the number one killer or males and females in America. People who
                    survive a heart attack have a 1.5-15 times higher chance of illness and death than the rest of the
                    population. Both men and women have a substantial risk of another heart attack, sudden death, angina
                    pectoris, heart failure and stroke. Successful treatment of chronic stable angina may prevent
                    myocardial infarction and death as well as reduce symptoms of angina and occurrence of
                    ischemia thereby improving the quality of life.
Disease State       Coronary artery disease (CAD), also called coronary heart disease (CHD), ischaemic heart disease, and
Definition          atherosclerotic heart disease, is the end result of the accumulation of atheromatous plaques within
                    the walls of the arteries that supply the myocardium. While the symptoms and signs of coronary
                    heart disease are noted in the advanced state of disease, most individuals with coronary heart disease
                    show no evidence of disease for decades as the disease progresses before the first onset of symptoms,
                    often a "sudden" heart attack, finally arise. After decades of progression, some of these atheromatous
                    plaques may rupture and (along with the activation of the blood clotting system) start limiting blood
                    flow to the heart muscle.

Patho-              Limitation of blood flow to the heart causes ischemia of the myocardial cells. When myocardial cells
physiology          die from lack of oxygen MI. This leads to heart muscle damage, heart muscle death and later
                    scarring without heart muscle regrowth.

                    Myocardial infarction usually results from the sudden occlusion of a coronary artery when a plaque
                    ruptures, activating the clotting system and atheroma-clot interaction fills the lumen of the artery to the
                    point of sudden closure. The typical narrowing of the lumen of the heart artery before sudden closure is
                    typically 20%, according to clinical research completed in the late 1990s and using IVUS examinations
                    within 6 months prior to a heart attack. High grade stenoses as such exceeding 75% blockage, such as
                    detected by stress testing, were found to be responsible for only 14% of acute heart attacks the rest
                    being due to plaque rupture/ spasm. The events leading up to plaque rupture are only partially
                    understood. Myocardial infarction is also caused, far less commonly, by spasm of the artery wall
                    occluding the lumen, a condition also associated with atheromatous plaque and CHD.


Clinical            Many episodes of ischemia do not cause symptoms of angina (silent ischemia).
Presentation
                    STABLE ANGINA
                        Chest pain or complaining of “heaviness, pressure, squeezing, discomfort, tightness, or
                         constriction”
                        Chest discomfort usually begins and ends gradually, is diffuse, and radiates
                        Precipitated by exertion, emotional upset, cold weather, or heavy meals.
                        Pain brought on by exertion usually abates 5-10 min after cessation of activity.
                        Some pts (elderly, diabetics) with stable angina may not present with pain, but with “anginal
                         equivalent’ symptoms such as shortness of breath, fatigue, dizziness, light-headedness, nausea,
                         or diaphoresis
                        Patients commonly have a normal PE (unless currently in chest pain: S4, paradoxically split S2,
                         or mitral regurgitation murmur may be noted)

                    UNSTABLE ANGINA
                       New-onset angina
                       Angina at rest
                       Increased frequency of angina
                       Increased severity of angina
                       Increased duration of angina
Molly Roberts, PharmD Candidate 2007                                  Pharmacotherapy Presentation – Pharmaceutical Care Rotation
University of Maryland School of Pharmacy                              Happy Harry’s Pharmacy Patient Care Center, Perryville, MD
                             Pain occurring with decreasing levels of exertion
                             Pain less promptly relieved with nitroglycerin
                             Patients commonly have a normal PE (unless currently in chest pain: S4, paradoxically split S2,
                              or mitral regurgitation murmur may be noted)

Risk Factors        Risk factors that can be modified:
                         Smoking: complete cessation; no exposure to environmental tobacco smoke
                         Blood Pressure: less than 140/90mmHg or less than 130/80mmHg if the patient has diabetes or
                            CKD
                         Lipid Management: LDL-C should be less than 100mg/dL, and it is reasonable to aim for a
                            level less than 70mg/dL. If triglycerides are equal to or greater than 200mg/dL, non-HDL-C
                            should be less than 130mg/dL, and it is reasonable to aim for a level less than 100mg/dL
                         Physical Activity: 30-60 minutes seven days a week (minimum five days per week)
                         Weight Management: BMI - 18.5 to 24.9 kg/m2; waist circumference – men less than 40
                            inches, women less than 35 inches
                         Diabetes Management: HbA1c levels less than 7 percent
                    Risk factors that cannot be modified:
                         Age: men older than 45 years old and women older than 55 years old are at a higher risk
                         Family History: heart disease diagnosed before age 55 in father or brother; diagnosed before
                            age 65 in mother or sister.
                    Potential risk factors:
                         High blood levels of C-reactive protein (CRP), which shows in the presence of inflammation.
Diagnosis           No single test to diagnose CAD.

                    EKG for any chest pain thought to be ischemic in etiology. Most pts with unstable angina have EKG
                    changes (most commonly ST segment depression and T-wave inversion).

                    In patients presenting with chest pain, a detailed symptom history, focused physical examination,
                    and directed risk-factor assessment should be performed. With this information, the clinician should
                    estimate the probability of significant CAD (i.e., low, intermediate, or high).

                    The following tests may be necessary:
                        Echocardiogram
                        Exercise Stress Test: useful in establishing diagnosis and provides prognostic info
                        Chest x-ray
                        Cardiac catheterization: gold standard of diagnosing CAD; however, very invasive
                        Coronary angiography
                        Nuclear heart scan
                        Fasting glucose test
                        Fasting lipoprotein profile
                        Hemoglobin

Desired             Stable Angina:
Therapeutic              Reduce risk of MI and death and thereby increase the “quantity” of life
Outcomes*                Reduce symptoms of angina and the occurrence of ischemia, which should improve the quality
                            of life
                    Unstable Angina:
                         Reduce risk of death or MI/(re)infarction
                         Immediate relief of pain/ischemia

                         ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a
*Reference of            report of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines Used          Guidelines
Molly Roberts, PharmD Candidate 2007                                  Pharmacotherapy Presentation – Pharmaceutical Care Rotation
University of Maryland School of Pharmacy                              Happy Harry’s Pharmacy Patient Care Center, Perryville, MD
Treatment           Non-Drug Therapy:
Options**               Eat a healthy diet to prevent or reduce high blood pressure and high cholesterol and to maintain
                          a healthy weight
(Non-drug and           Quit smoking, if you smoke
Drug Therapy            Exercise, as directed by your doctor
– include all           Lose weight, if you are overweight or obese
therapeutic             Reduce stress
classes/agents          For the first time, flu shots are recommended in patients with chronic cardiovascular disease.
available and           Treat underlying medical conditions that may aggravate myocardial ischemia such as
preferences               hypertension, tachycardia, fever, thyrotoxicosis, anemia, or hypoxemia
per treatment           Modification of activities that exacerbated angina (cold weather, postprandial exercise)
guidelines)
                    Drug Therapy for Stable Angina:
                        Aspirin/Antiplatelet therapy
                        BB
                        CCB
                        Nitroglycerin
**See Treatment         Long-acting nitrates
Options Table
                    Drug Therapy for Unstable Angina:
                        Bed rest with continuous ECG monitoring for ischemia and arrhythmia detection in patients
                           with ongoing rest pain
                        Aspirin/antiplatelet therapy
                        NTG
                        Supplemental O2
                        Morphine PRN
                        BB
                        ACEI
                        Nondihydropyridine CCB (verapamil or diltizem)

                    Additional Treatment of Risk Factors:
                         Treatment of hypertension according to JNC VI
                         Management of diabetes
                         LDL-lowering therapy in patients with documented or suspected CAD and LDL cholesterol
                            greater than or equal to 130 mg/dL, with a target LDL of less than 100mg/dL
Monitoring          Indices of Therapeutic Effect:
                    Stable Angina:
(Efficacy and            Decrease frequency of chest pain and TNG administration
Toxicity                 Increase exercise tolerance
Parameters)
                    Unstable Angina:
                        Relieve chest pain and improvement of pattern of pain
                        No evolution to MI

                    For complete monitoring parameters for individual agents/classes see Pharmacological Treatment
                    Options Chart.




Molly Roberts, PharmD Candidate 2007                               Pharmacotherapy Presentation – Pharmaceutical Care Rotation
University of Maryland School of Pharmacy                           Happy Harry’s Pharmacy Patient Care Center, Perryville, MD

				
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posted:10/19/2011
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