The Noninvasive Heart Center
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DRUGS USED TO TREAT HEART DISEASE AND WHY THEY ARE NECESSARY*


ALTERNATIVES TO BYPASS SURGERY AND ANGIOPLASTY

In those patients in whom there is significant narrowing of one or more coronary arteries, the heart muscle will remain chronically deprived of blood flow and oxygen. If the reduction in blood flow is large enough, the heart muscle will die and be replaced by a scar. If the reduction in blood flow is not enough to destroy the muscle, then the muscle will be able to survive and function to a limited degree. In the final analysis, both survival and function depend upon two things: blood flow and work load. The situation is very comparable to our daily living. How much money we have at the end of the month depends upon income and expenses. If our income decreases, to maintain the same lifestyle, we have to increase our income from another source. If that cannot be done, we have to cut back on our lifestyle by reducing expenses.

In the case of the heart, income can be equated to blood flow bringing in the necessary oxygen. Drugs are available to increase that blood flow by dilating the coronary arteries. Expenses can be likened to the load the heart has to work against; that is, any physical or emotional strain that causes the heart to labor more. High blood pressure would be an example of an increased work load.

Most drugs used for the treatment of coronary artery disease either reduce the work load on the heart, or they increase the blood supply. How effective one approach is compared to another depends entirely on the clinical situation. As a general rule, work load reducing drugs tend to be more effective than medications that increase the blood flow to the heart muscle.


WORK LOAD REDUCING DRUGS

There are several classes of drugs which will accomplish this. They include beta blocker drugs, calcium channel blockers, diuretics, and so called ACE inhibitors.

Beta Blockers

The prototype drug in this class is Inderal. This drug has been available for over 25 years and is the most effective of all the beta blockers. It combines with chemical receptors on the surface of the heart known as beta-adrenergic receptors. These receptors are chemically structured in such a way so that they can combine with certain adrenalin-like hormones secreted by the body. These hormones are naturally discharged whenever the heart has to increase its rate, or its force of contraction. This will quickly produce chest pain in individuals with obstructive coronary artery disease.

Beta blockers act by combining with the chemical receptors on the heart's surface, prevent the increase in heart rate caused by adrenaline-line hormones. The final outcome is one in which the heart does not require as much oxygen or blood flow to the heart muscle as it did before the use of beta blockers, and chest pain is prevented.

Beta blockers like Inderal have been shown to protect the heart from future heart attacks, and to reduce mortality in patients after a heart attack, when given on a chronic basis..

Calcium Channel Blockers

An entirely different class of drugs than the beta blockers are the calcium channel blockers. These drugs act by relaxing the muscular walls of all arteries including the coronary vessels. Relaxation of the musculature of a coronary artery will increase its diameter enabling it to carry more blood and oxygen to the heart muscle. In addition, since the arteries throughout the body also are affected, there will be a decrease in the resistance to the flow of blood, and a fall in blood pressure. The final effect will be a reduction in the work the heart must do, and a decrease in its need for oxygen.

Commonly used calcium channel blockers include Cardizem, Procardia, and Norvasc. The advantage of the calcium channel blockers is its dual effect of lowering blood pressure, and increasing coronary blood flow. In general, the calcium channel blocking agents are highly effective, safe, and when used with care, can be depended upon to provide considerable benefit in most patients who are symptomatic.


DRUGS WHICH INCREASE BLOOD FLOW TO THE HEART

Nitroglycerine and Nitrates

Nitroglycerine and nitrates have been used to treat patients with chest pain (angina pectoris) due to coronary artery disease for over 100 years. Two kinds of nitroglycerine drugs are available. One is nitroglycerine available in various forms including sublingual tablets, an ointment, patches and an oral spray. The other preparations are generally referred to as nitrates and consist of tablets that are chewed or swallowed. The most commonly used drug is Isordil or isosorbide dinitrate.

Nitroglycerine and nitrates act by dilating the veins and arteries of the body. Since they preferentially enlarge the caliber of the veins, there is an increase in the blood carrying capacity on the venous side of the circulation. The result is a reduction in the amount of blood returning to the heart, a decrease in the volume of blood within the heart's chambers with each heart beat, and a fall in pressure. In the same way that less air within a balloon brings about less expansion and tension, so is there less pressure and tension within the heart muscle. Accordingly, there is less compression of the microcirculation and an increase in coronary blood flow. Nitroglycerine and nitrates also relax the muscle within the walls of arteries throughout the body including the coronary vessels. Not only does this directly increase coronary blood flow, but it lowers blood pressure and the amount of work that the heart must do.

The most popular form of nitrates besides Isordil are Sorbitrate, Cardilate, Dilatrate, and Peritrate. Various form of nitroglycerine skin patches also are used and include Minitran, Nitro-Dur and Transderm-Nitro.

Diuretics

Most doctors use only beta blockers, calcium channel blockers and nitrates in the treatment of angina pectoris. Few seem to be aware that one of the most effective of drugs in this condition are diuretics. Diuretics are drugs that aid in the elimination of fluid by the kidney. They are essential in the treatment of high blood pressure.

There are sound reasons for using diuretics in the treatment of patients with chest pain or shortness of breath with exertion, even in the absence of high blood pressure. All of the drugs conventionally used for the relief of angina tend to cause fluid retention. Since such fluids are equally distributed throughout the body tissues, this can have a profound influence upon the efficacy of the most useful of the anti-anginal medications, the nitrates. Nitrates act, in part, by dilating the veins of the body. To be absolutely correct, the term venules and small veins should be used since nitrates do not act upon the larger veins. Venules refer to the smallest veins in the circulatory system through which blood flows immediately after it leaves the capillaries. There are a tremendous number of such venules in the body, and they are capable of storing a considerable amount of blood. Such tiny vessels have no protection as do the arteries. There are no muscular fibers within their walls to resist compression or collapse. Consequently, they are quite susceptible to such compression whenever fluid retention causes the tissues of the body to swell. Doctors call such tissue swelling edema.

A great deal of edema must be present before a person is aware it is even there. The best example is in the swelling that occurs in our feet and ankles on long trips. Our shoes feel tighter and our feet swollen. Were it not for prolonged periods of dependency, we would never be aware that such fluid retention was taking place. The tightness we experience reflects the increase in pressure within the tissues. A similar increase in tissue pressure is present whenever there is edema, although we may not be aware of it. Women tend to be more familiar with this feeling than men because of premenstrual fluid retention. The female breast tends to be fuller and more tender in such circumstances.

The increase in tension and pressure within the tissue from fluid retention is sufficient to compress venules and small veins wherever it exists. If enough venules are compressed, the reservoir function of these vessels is eliminated. As previously described, nitroglycerine drugs work as they do because venules capture and store significant amounts of blood, which reduces the volume of blood entering the heart. The fall in pressure that follows, decreases the heart's work, and increases coronary blood flow. Therefore, whenever there is fluid retention, the effectiveness of nitrates is lost. Indeed, this may be one of the mechanisms to account for the development of tolerance to these drugs.

In addition to the fluid retention caused by beta and calcium channel blockers and nitrates, it may develop for other reasons. For example, fluid retention may be seen after stress, during urinary tract infections, and following the use of certain drugs used for pain relief. This latter group of drugs is often referred to as the nonsteroidal, anti-inflammatory drugs or NSAIDS. Fluid retention also may be noted after excessive food or fluid intake.

Such fluid retention is extremely common, and most victims are totally unaware it is present. While the evidence of such fluid retention can be identified by certain noninvasive tests, in most cases it cannot be detected by a doctor, even when the subject is aware that it is present. The signs are recognizable by those familiar with it, and include mild puffiness under the eyes, some difficulty in removing rings from the fingers, a feeling that shoes are tight, and a tightness of snug fitting clothes. Typically these are subjective feelings experienced by the patient and not objective signs that a doctor will notice. Nevertheless, they are important barometers that fluid retention exists.

Diuretics can prevent all this from happening. Usually it is necessary to take them both morning and evening. When this is done, regardless of the cause of the fluid retention, diuretics will eliminate the excess fluid from the body. Because diuretics also help to lower the blood pressure, these drugs, when used with other anti-anginal medications, are extremely effective in relieving symptoms.

ACE Inhibitors

Another group of drugs that may be effective in angina patients is the angiotensin converting enzyme inhibitors, more popularly referred to as the ACE inhibitors. Angiotensin is a hormone produced by the body, and it has the ability to elevate blood pressure. In order for this hormone to work, a converting enzyme is necessary to change its structure. ACE inhibitors prevent this from happening. Strictly speaking these are not anti-anginal drugs. However, they are highly effective in lowering the blood pressure. One of the goals of anti-anginal therapy is to lower pressure to minimize the work of the heart. Unfortunately, many doctors still cling to the old concept that a pressure of 130-140/75-85 is normal, and need not be of concern. Whether these numbers are normal is not the issue---what is overlooked is that a normal blood pressure is too high for someone with heart disease. Experience has shown that the patient with a low blood pressure has less chest pain and fewer heart attacks. Accordingly, the pressure should be reduced to the lowest level possible, as long as it doesn't interfere with the patient's activities. Furthermore, what is usually overlooked by physicians who believe values of 130-140/75-85 are normal, is that these numbers represent resting blood pressures. With stress, blood pressure can easily rise in seconds to 175/100, a value everyone would agree is abnormal. On the other hand, if the pressure is 105/70, and is carefully controlled with medication, stress is not likely to elevate the pressure. Even if it does, it will not be more than 10-15 millimeters of mercury. Clearly, it is less work for the heart if the pressure only rises to 115/80 compared to 175/100.

The prototype ACE inhibitor is Capoten. Vasotec is another useful drug. Unfortunately, both these medications have to be taken twice a day. Newer ACE inhibitors such as Zestril or Prinivil, Lotensin, Altace and Monopril only have to be taken once a day and are extremely effective.


Who Should Be Treated

While the problem of taking anti-anginal drugs to obtain relief of symptoms seems straight forward enough, and is not controversial, it is not so simple as it seems. Some background information is necessary for you to understand what is to follow. The matter involves the question as to whether a reduction in blood supply to the heart muscle always causes symptoms, and if so, how often does this occur, and is it potentially harmful? The medical term for this is ischemia.

When ischemia is mild, there may be no symptoms if it is brief. Even moderate to severe ischemia may not produce chest pain if the duration is only for a few minutes. If it lasts for 15-20 minutes, not only is pain likely to occur, but there probably will be some mild, reversible injury to the cardiac muscle. Ischemia for more than 30 minutes is apt to produce a heart attack---myocardial infarction in medical terminology, with irreversible damage to the muscle.

Up until the early eighties, there was little awareness of how frequently ischemia existed in patients with coronary artery disease, in the absence of chest pain. Studies at that time with the 24 hour EKG monitoring system known as the Holter monitor, demonstrated that cardiac ischemia was far more prevalent than anyone had ever realized. Not only was it more frequent, but 75% of all episodes were silent. Up until this time, the conventional wisdom was to give antianginal drugs only to people to relieve symptoms. If symptoms were abolished, then nothing further had to be done. The fact that many, if not most patients with coronary artery disease were experiencing ischemia without pain, changed the way heart disease had to be treated. The discovery of silent ischemia, as it came to be called, was a major turning point, particularly when it was recognized that silent ischemia might last for many hours every day. Why the ischemia is silent has never been adequately explained, but it will occur in most patients, even in those who also have symptoms.

The question that needs to be answered is whether silent ischemia should be treated, and if so, how intensively? The problem will not be easy to solve. At least when symptoms are present, the doctor can easily determine if the patient's medical program is adequate. If it is, then symptoms will disappear. If it isn't, the patient will continue to have chest pain. In the absence of symptoms, there will have to be other guide lines to determine success or failure. One approach would be to repeat the Holter Monitor at regular intervals; however, this can become costly and is time consuming. Additional ways to determine if the functional status of the heart is improving were discussed in the previous chapter. Whatever approach is used, it is just as important for silent ischemia to be avoided as it is for symptomatic ischemia.

What might be the advantages of treating silent ischemia? Indeed, why is it even necessary, as long as it is not disturbing the patient? Chest pain is not the only symptom, nor even the most frequent indication of coronary artery disease, but it is the one that gets the most attention. Far more prevalent is fatigue of the exertional variety. Typically, patients find that they may be able to do what they always did, but not for as long. They just get tired. After an appropriate rest, the activity can be resumed. Many individuals learn to avoid those efforts that produce fatigue. Except in extreme cases, usually this is not an inconvenience. Unfortunately, this leads to gradual deconditioning of the entire body with a negative impact on cardiovascular function. In fact, ultimately, more patients are limited by their deconditioned state than they are by their cardiovascular disease. Accordingly, any medication that will improve blood flow to the heart, or decrease the heart's work load, will increase exercise tolerance and help prevent the vicious circle of deconditioning.

The second reason why silent ischemia should be treated is to prevent the progression of the complications of chronic cardiac ischemia. Whenever there is damage to a segment of heart muscle, and it is unable to move, the segment on the opposite muscular wall will compensate by contracting more forcefully. In this way the same amount of compression of the heart's chamber takes place, but one wall of the heart may have to move twice the distance as it once did. In time this causes the harder working segment to stretch, and the heart to enlarge. Whenever this happens, the work of the heart increases, stimulating further stretching and enlargement. Eventually, the muscle loses its elasticity, and the heart begins to fail. Once heart failure begins, most patients will die within just a few years.

It would seem logical that prevention of ischemia would prevent this cascade of events from taking place. In fact, that is exactly what occurs. In patients on a full medical program designed to minimize or eliminate ischemia, particularly of the silent variety, there is a dramatic reduction in the complications of chronic ischemic heart disease. Heart failure rarely occurs, the incidence of recurrent heart attacks is very low (1-2% per year), and mortality rate is also extremely low (1-1.5% per year). Because the progression of the disease is extremely slow on such a program, more heroic treatments such as bypass surgery or angioplasty are needed only rarely. A good medical program will allow a patient to be symptom free and enjoy a normal life span. Whether this happens or not depends entirely on the ability of the cardiologist to identify patients with silent ischemia who stand to benefit the most from a medical program similar to the one described in this chapter. Patients who have symptoms will be treated, for they demand attention. It is those without symptoms who have the most to gain, and the most to lose if they are ignored. If you have coronary artery disease, your survival will largely depend upon whom you chose to treat you. So choose well!

Howard H. Wayne, M.D., F.A.C.C., F.A.C.P.
Excerpts from How to Protect Your Heart From Your Doctor