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
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
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
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.
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
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
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
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
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
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