Coronary artery disease treatment

Author : Dr Kendrick Shunk Interventional Cardiologist University of California San Francisco (UCSF) School of Medicine

2008-10-24

Coronary Artery Disease : Treatment. Coronary artery disease (CAD) is a common condition. The best combination of treatments depends upon several factors. This article focuses on the rationale behind the most common treatment strategies.

If you think you may be having a heart attack, dial 911 immediately.  Here are warning signs: American Heart Association

Contents

• Introduction

• Scope of the Problem

• Goals of Treatment

• CAD screening

• Stable Angina

• “Lifestyle”, Diet, Exercise, Tobacco

• Aspirin and clopidogrel in stable CAD

• Cholesterol lowering drugs in stable CAD

• Anti-anginal drugs in stable CAD:

• Acute Coronary Syndromes (ACS):

• Aspirin and clopidogrel in ACS:

Coronary artery disease (CAD) is also known as Coronary Heart Disease (CHD) to emphasize the impact on the whole heart.  CAD is a common condition in the United States and other developed countries.  The best combination of treatments for this condition depends heavily upon the setting in which the condition is recognized or diagnosed.  This article focuses on the rationale behind the most common treatments and outlines the considerations that patients and health care providers should keep in mind when creating and optimizing a treatment strategy.

Introduction:

Understanding the rationale behind therapy for CAD requires a brief explanation of the way that CAD presentations are classified by cardiologists and other health care providers.  Much is available elsewhere (link, AHA) on the basic biology leading to CAD.  This knol provides an overview of certain considerations that bear on the process of creating an individualized plan for CAD therapy. 

Classification of CAD according to how it manifests:
Coronary Artery Disease (CAD) makes its presence known in a variety of ways.  Cardiologists classify the disease along a spectrum, depending on how it presents, dividing it into three main types:
 

1. acute coronary syndromes
2. stable angina
3. asymptomatic CAD (not causing symptoms) 

Acute coronary syndromes are the most urgently concerning and they are, in turn, divided into three major subtypes:
  a.  Unstable angina
  b.  Non-ST segment elevation myocardial infarction
  c.  ST segment elevation myocardial infarction

The latter two are both considered “heart attack” according to the recently published updated definitions of myocardial infarction (heart attack).  They are distinguished primarily by findings on the electrocardiogram (abbreviated ECG or EKG).

Scope of the problem:

Each year in the United Stated there are 1.57 million hospital admissions for acute coronary syndromes.  For some of these people, this is their first manifestation of CAD, while others are among the 6.2 million Americans already diagnosed with stable CAD.  An estimated 1.5 million people are newly diagnosed with stable CAD each year.  Perhaps more disturbing, for some people, the very first symptom of CAD can be death; it is estimated that 550,000 Americans who experience an acute coronary syndrome die without ever reaching a hospital.

Goals of Treatment:

A brief word on why we treat CAD (or any condition for that matter):
There are really only two valid reasons to apply a particular treatment to an ailment:
1) If it can be expected to extend life, and/or
2) If it can be expected to improve the quality of life.

Fortunately, in the case of coronary artery disease, there are several medications and procedures supported by scientific evidence in clinical trials for one or both of these benefits.

The specific therapy combinations most appropriate for CAD depend heavily on which of these scenarios pertains.  Certain strategies are appropriate across the board and others are more appropriate for only a particular subset of people with CAD.  As a reminder, this is an overview and clinical judgment still has a major role.  Decisions regarding the specific care plan for a particular patient must always be made by the healthcare provider and patient in partnership, taking into account the whole picture.

CAD screening:

This pertains to patients who have not had any manifestation of CAD.  In light of the growing use of CAD screening tests, two new recommendations have recently emerged from the American Heart Association that bear on the issue of screening for the presence of CAD in patients who may not have any symptoms:

1) Your primary care provider should be evaluating you for the presence and status of control of major risk factors for CAD at regular intervals (approximately every 3 to 5 years).

2) If you have 2 or more major risk factors, you and your provider should calculate your risk of heart attack within the next 10 years using the Framingham risk calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp ) to assess the need to implement specific strategies to reduce the risk of having a first heart attack.

Other screening strategies, including imaging tests, may be appropriate in some circumstances, but this remains controversial. 

Stable Angina:

If you already carry a diagnosis of stable CAD, you should be screened for factors that may contribute to subsequent heart attack(s).  Certain patients who have never actually manifested CAD, but who have other high risk conditions are considered to have a “CAD equivalent” in terms of their risk of heart attack.   These conditions include cholesterol plaques (atherosclerosis) in other blood vessels such as the arteries supplying the head (carotid arteries), kidneys (renal arteries) or legs (iliac or femoral arteries), diabetes, chronic kidney disease, or a Framingham risk score of > 20%.   People with CAD equivalents should be treated with equal intensity as patients with known CAD in terms of risk factor interventions.

In the vast majority of CAD cases, the problem is one of abnormal cholesterol deposition in the cells that line the walls of arteries, producing atherosclerosis.  In the case of “stable angina” or non-ACS presentations, this cholesterol deposition can lead to progressive narrowing of the size of the flow channel in the coronary artery, with resulting decrease in the maximum capacity for oxygen delivery to the heart muscle.  The normal response to increased demand on the heart such as with exercise or emotional stress, is for the arteries to relax and enlarge (dilate) to allow increased flow of oxygenated blood to the heart muscle.  With the cholesterol buildup in the artery wall, the vessel becomes less and less capable of dilating in response to any increase in demand and the result is that these episodes of increased demand produce a significant lack of oxygen in the area downstream of the cholesterol blockage.  This condition of inadequate oxygen in the heart muscle is known as myocardial ischemia. 

This typically results in angina pain that is often referred to as a dull pressure sensation and may radiate to the neck, jaw, shoulder, or elsewhere.  In some cases, angina pain does not follow the typical patterns and can be easily confused with other types of pain (for example toothache), but the tip-off is usually that it comes on with exertion and goes away with rest.  Other tip-offs include the presence of certain accompanying symptoms, such as a cold sweat (diaphoresis), nausea, or shortness of breath.  In some people, myocardial ischemia may produce no symptoms at all, but this condition—known as silent ischemia—is no less worrisome.  In fact, it may be more so, since the lack of symptoms can make it more difficult for health care providers to assess whether anti-ischemia treatments are working. 

Stable angina can have a major impact on quality of life and puts one at risk for development of an acute coronary syndrome.
Evaluation of the person with stable angina usually involves a stepwise approach, starting with the least-invasive, least-expensive, and least-risky evaluations.  This generally means a history and physical exam to identify related conditions such as hypertension (high blood pressure).  Often in that first wave of evaluations there is an assessment of the baseline electrocardiogram and cholesterol profile by means of a specific blood test done while the person is fasting.  This helps to identify abnormalities that could be contributing to the problem and can help prioritize treatment strategies when there are multiple abnormalities.  It may be appropriate to perform additional non-invasive testing such as echocardiography (link to Foster), or cardiac stress testing (link to Botvinick), depending on the findings of the initial evaluation.  It may also be appropriate to perform coronary angiography to further characterize the disease and assess the risk for subsequent problems such as myocardial infarction (heart attack) and death.  Much of the evaluation is aimed at determining this risk, and therapeutic goals are frequently aimed at reducing this risk and improving symptoms.

Options for treating stable angina are many and are usually applied in concert.

“Lifestyle”, Diet, Exercise, Tobacco

The American Heart Association offers numerous recommendations aimed at CAD patients, including recommendations for changes to diet and lifestyle  as well as exercise .  Aerobic exercise of a moderate intensity for ~30 minutes at least 5 times a week or of high intensity for >20 minutes at least 3 times a week are helpful.  Diet is a more complex subject but at a minimum should emphasize no more than appropriate total caloric intake with low saturated fat and dietary cholesterol content, trans-fat intake of <1% of total calories, and for most people an increase in non-processed foods such as fresh fruits and vegetables and whole grains.

Tobacco is a major contributor to CAD and tobacco cessation is of critical importance for anyone with CAD.

Aspirin and clopidogrel in stable CAD:

As long as you do not have an allergy or other significant problem with aspirin, it is recommended to reduce the risk of heart attack.  The typical dose can be anywhere from a single baby aspirin (81 mg) to a full strength adult tablet (325mg) once a day, depending on the recommendation of your provider who will take into consideration other risks, such as bleeding.  For those who do not tolerate regular aspirin due to stomach upset, enteric-coated aspirin is recommended.  When aspirin absolutely cannot be taken, clopidogrel (75 mg per day) is an alternative.

Cholesterol lowering drugs in stable CAD:

Frequently these “lifestyle” interventions alone are insufficient to adequately reduce risk and a specific cholesterol lowering medication is prescribed.  Numerous large clinical trials have demonstrated the benefit of many of “statin” agents in reducing low density lipoprotein (LDL) or “bad” cholesterol levels and/or the risk of subsequent heart attacks in patients at risk.  Statins are also known as HMG CoA reductase inhibitors.  They work by inhibiting a key step in every cell’s own internal cholesterol manufacturing process as delineated in large part by two scientists-- Michael Brown and Joseph Goldstein-- who received the Nobel prize for their work in unraveling how cells do this.  Since cells cannot live without cholesterol, they are forced to increase the number of LDL receptors on their surface in order to obtain their cholesterol from the bloodstream.  The level of LDL in the blood then drops and this helps prevent further deposition in the walls of arteries.  Brown and Goldstein’s work led to the development of the first statin.  Numerous statins are now approved by the FDA and are available in the US and elsewhere.  Some are more powerful than others and each has its own risk profile (including one—Cerivastatin—which was removed from the market in August 2001 for a non-favorable risk profile). Nonetheless, as a group they share the property of lowering LDL or “bad” cholesterol.  The currently available statins in the US (in alphabetical order, by generic name) are:

• atorvastatin
• fluvastatin
• lovastatin
• pravastatin
• rosuvastatin
• simvastatin

A full set of guidelines relating to cholesterol management is available from (http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf) including discussion of alternatives to statins. In summary, most cardiologists believe that anyone who has documented CAD should take an appropriately aggressive type and dose of statin.  The maximum goal LDL should be <100mg/dl and treating LDL down to <70 is highly desirable.  This is often not accomplished right away after a manifestation of CAD, but may require working with your cardiologist or primary care provider over a period of time.  There is also evidence that even when LDL cholesterol levels are not elevated at baseline, statins reduce the risk of an initial or repeat heart attack (and stroke) in patients with CAD or CAD equivalent.  

Anti-anginal drugs in stable CAD:

By reducing the heart rate and blood pressure, anginal symptoms are often controlled.  The key medicines for this are the Beta Blockers.  These drugs interrupt the natural pathways for increasing the heart rate and force of contraction, resulting in lower heart rate and blood pressure.  The most commonly used beta blocker for this purpose is metoprolol since it is available in intravenous form as well as short and long acting pill forms, and has strong data to support its use for this purpose.  Atenolol is frequently used as well.  The list of beta blockers available in pill form in the US is shown by generic name:

• acebutolol
• atenolol
• betaxolol
• bisoprolol
• labetalol
• metoprolol
• nadolol
• penbutolol
• propranolol
• timolol

In addition to the beta blockers, nitrates are effective and recommended for relief of angina.  In the hospital they can be given as nitroglycerin or as a paste that absorbs through the skin.  Patients with CAD should carry sublingual (under the tongue) nitroglycerin tablets (0.4mg) or spray to be taken under the tongue if chest pain develops.  For patients with stable CAD, who have occasional episodes of chest pain in a predictable pattern, this may be repeated every 5 minutes for a total of 3 nitroglycerin tablets (or sprays) to attain relief.  Failure to produce complete relief may mean that you have now developed an acute coronary syndrome and should prompt an immediate 911 call.  This differs for patients with angina that is not following its usual pattern—if this happens, you should not wait more than 5 minutes before calling 911, as it likely represents an acute coronary syndrome.  Long acting nitrates may also have a role for some patients with stable CAD.

For patients who are having angina despite beta blocker and whose blood pressure is still elevated, adjunctive anti-anginal medications are employed, including certain calcium channel blockers.  Also, for patients who cannot take a beta blocker at all, certain calcium channel blockers make an acceptable alternative. (Specifically, calcium channel blockers that are both short-acting and members of the dihydropyridine chemical class are usually avoided for control of angina in place of or in addition to beta blockers because of unacceptable side effects/risks). 

If the pumping function of the heart is impaired such that you have either signs or symptoms of congestive heart failure or a reduced ejection fraction, an angiotensin converting enzyme or ACE inhibitor is recommended.  If you do not tolerate an ACE inhibitor (20% of people started on an ACE inhibitor develop a bothersome cough), an angiotensin receptor blocker or ARB is an acceptable alternative.

For those who do not have anginal relief with medical therapy, or who have certain other high risk features, revascularization via invasive techniques may be appropriate.  The two main types of revascularization, coronary bypass artery grafting and stenting, are described below. It must be kept in mind, however, that while revascularization is highly effective for reducing symptoms of angina and thereby improving quality of life, it has not been demonstrated to prolong life in the case of people with stable CAD (as it has with acute coronary syndromes).

A 2007 update to the recommendations for treatment of stable angina, written for healthcare providers, but in somewhat accessible language is available as a pdf.

Acute Coronary Syndromes (ACS):

Acute coronary syndromes are fundamentally different from stable CAD.  Typically, instead of the slow and gradual progression of atherosclerosis associated with stable CAD, acute coronary syndromes result from plaques becoming inflamed-- not unlike a case of arterial acne flare.  These inflamed plaques can rupture suddenly and expose their contents to the bloodstream.  This, in turn, causes the blood to clot onto the ruptured plaque, and the resulting clot usually leads to new angina in the case of someone who has not had it previously, or to a change in the severity, threshold, or other features of angina for someone who previously had stable CAD.  If the sudden obstruction is severe enough, it may lead to a myocardial infarction --a heart attack. The two subtypes of myocardial infarction (heart attack) are called non-ST segment elevation myocardial infarction and ST segment elevation myocardial infarction.  They are identified and distinguished by the presence or absence of a particular finding on the electrocardiogram (abbreviated either ECG or EKG), which should be obtained immediately in patients with suspected acute coronary syndrome.

The treatment principles described for stable CAD apply to acute coronary syndromes, however the priorities change somewhat, the urgency is much higher, and some additional therapies are added to the mix. 

Aspirin and clopidogrel in ACS:

Therapy is as above for stable CAD, except that the aspirin is more typically given as a full strength (325 mg) tablet, and is chewed immediately upon onset of the acute coronary syndrome or upon arrival of emergency personnel or, failing that, upon arrival to the emergency department.  Clopidogrel remains the alternative if aspirin cannot be taken.  In addition, clopidogrel is often given together with the aspirin unless there is high suspicion that bypass surgery will be needed.

Anti-anginal drugs:
A beta blocker is employed as described above except that it is typically given immediately by intravenous route and then switched to pill form at the appropriate time (usually by ~24 hours)

Nitroglycerin is recommended and is commonly given by intravenous infusion for relief of angina. 

Inhaled oxygen by way of mask or nasal “prongs” is appropriate initially in all patients and is often continued for ~6 hours or until adequate myocardial oxygenation is assured.

Morphine by intravenous injection is often appropriate for patients who do not have complete pain relief with nitroglycerin.

Because all of these medicines can cause the blood pressure to fall, it may not be possible to start other drugs that affect the blood pressure, but for patients who can tolerate it, ACE inhibitor is recommended.  Again, ARB is an acceptable alternative

For patients who are still having angina despite all of the above and are maintaining adequate blood pressure, a calcium channel blocker is sometimes added, although less frequently than with stable CAD.

For those who do not have prompt anginal relief with all of the above interventions or for those who develop severe heart dysfunction (cardiogenic shock), an intra-aortic balloon pump or IABP can be used to augment coronary blood flow and aid the pumping function of the heart until more definitive therapy can be employed. 

In contrast to stable CAD, acute coronary syndromes often mandate an “early invasive approach” with cardiac catheterization and coronary angiography to define status of the coronary arteries and help inform a strategy of revascularization, if needed.  This has been shown to improve survival in most cases of ACS compared to the “watch and wait” or conservative management approach Exceptions to this include patients without any high risk features (link to TIMI risk score?) in which case patient and/or physician preferences for a conservative strategy can prevail without demonstrable harm.

Timing:
Most cases of acute coronary syndromes are on a tempo of hours, while a special case (ST elevation myocardial infarction, identified on the electrocardiogram), mandates a tempo on the order of minutes.  Treatment must proceed at a rapid rate for the best chance of survival and the target time from arrival in the emergency department to re-establishment of adequate blood flow should be <90 minutes.  For this to happen, each of the many steps involved must occur without delay.  Specific considerations in the management of ST elevation myocardial infarction is a separate subject (link)

Cholesterol lowering drugs in ACS:
Recommendations are similar to those suggested for stable CAD above, except that the treatment goals are often more aggressive (goal LDL of <70) and it should be emphasized that early treatment is beneficial.  Ideally no patient who is hospitalized for an acute coronary syndrome should leave the hospital without a statin unless he or she has an absolute inability to tolerate one, in which case alternative cholesterol lowering strategies should be employed.
(http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf)


Revascularization:
Besides the medical therapies mentioned already, there are additional invasive or surgical options available to provide more oxygenated blood flow to the myocardium for many people with CAD. The two main methods of revascularization are discussed below.  Briefly, the plaque narrowing(s) in the coronary artery(ies) can either be bypassed with a piece of artery or vein taken from elsewhere in the body, called coronary artery bypass grafting (CABG), or the vessel can be re-expanded, typically with a balloon and a small wire mesh implant called a stent.  Most of the evidence for benefit of these therapies in prolonging life comes from studies of patients with acute coronary syndromes, particularly those with myocardial infarction (heart attack), rather than stable CAD or asymptomatic CAD. However, there is ample evidence that quality of life (freedom from angina) is effectively improved in both stable and acute coronary syndromes.  In stable CAD patients who are without angina or related symptoms once adequate medical therapy is employed, revascularization can safely be deferred without increasing risk of death, however, for patients with angina that is not controlled with medications, revascularization should be considered.  In the case of ongoing myocardial infarction, revascularization can be truly life-saving.



CABG
Coronary artery bypass grafting (CABG) requires a surgical incision and a typical recovery time of weeks to months, although advances with smaller incisions and new devices such as stabilizers and surgical robotic assistants are allowing smaller and smaller incisions and potentially faster recovery times.  CALL OUT TO THE IMAGE This method of revascularization was the first one available and as such has the longest track record.  It is often the method of choice when there are multiple blockages or narrowings, or when they occur in particularly risky locations.  This method is less appropriate for patients who have recently had a large myocardial infarction or for other reasons might not tolerate a major operation.  For more information (link to other knol of mine or Ed’s)

Stenting
Coronary artery angioplasty and stenting (also known as percutaneous coronary intervention (PCI)  is typically performed entirely through a small catheter inserted into the femoral artery in the groin, near the crease separating the upper thigh from the lower belly.  The hole in the skin is approximately the size of a pencil. (link to cath knol)



Additional resources:

Working in conjunction, the American College of Cardiology and the American Heart Association (AHA), issue numerous relevant guidelines that pertain to CAD.  In many cases, other societies have signed on as well. 

The AHA site in particular has numerous resources for patients as well as physicians.  Some other professional society sites also contain content written in language that may be relatively accessible to patients and the non-professional seeking to learn more.

www.americanheart.org
www.acc.org
http://www.scai.org