Key Words: Non
Interventional Management, Coronary Artery Disease
In India, among adults over the age of 20 the prevalence of
Coronary Artery Disease (CAD) is about 3 - 4 percent in rural
areas and 8 - 10 percent in the urban areas [1]. Indian
migrants in various parts of the world also have shown an
increase in susceptibility to CAD when compared to the native
population [2]. The management of Coronary Artery Disease has
seen a sea change over the years. The management of the
condition is mainly interventional in most centers now where
the facilities are available. But the non-interventional
management is also of equal importance, especially in a few
subsets of patients as we shall see subsequently.
Presentation of coronary artery disease [3]
The presentation of coronary artery disease (CAD) varies from
patient to patient and from time to time in the same patient.
There are many presentations and combinations of two or more
clinical presentations are also possible. The main
presentations of CAD are as follows:
1. Asymptomatic Ischemia
2. Chronic Stable Angina Pectoris
3. Acute Coronary Syndrome (ACS)
a. Unstable Angina Pectoris
b. ST elevation myocardial infarction - STEMI
c. Non-ST elevation myocardial infarction - NSTEMI
4. Cardiac Failure - Ischemic
Cardiomyopathy
5. Arrhythmias
6. Sudden Cardiac Death
Chronic stable angina
The symptoms of chronic stable angina (CSA) are only too well
known. In the medical management of CSA the main emphasis in
on goal directed therapy aiming at preventing death and
myocardial infarction and also controlling the signs and
symptoms of myocardial ischemia to give the patient a
reasonably good quality of life. It is with these aims that
the therapy of CSA is planned.
Non Invasive Risk Stratification of CAD [4]
In the management of CSA, patients can be divided into three
categories according to the risk. They are as follows:
1. High Risk with and Annual Mortality Rate more than 3% :
Severe resting left ventricular (LV) dysfunction
(EF < 35%)
High Risk Treadmill stress test
Severe Exercise LV dysfunction ( Ex. LVEF < 35%)
Stress induced single large perfusion defect on myocardial
perfusion studies
Stress induced multiple perfusion defects
Echo wall motion abnormality in more than two segments with
low dose dobutamine
Stress echo evidence of severe ischemia
Large perfusion defect with LV dilatation
2. Intermediate Risk with Annual Mortality Rate of 1%
- 3% :
Mild to moderate resting LV dysfunction (EF = 35 -
49%)
Intermediate risk Treadmill stress test
Stress induced moderate perfusion defect without LV
dilatation
Limited stress echo ischemia with a wall motion abnormality
of < 2 segments with high dose dobutamine
3. Low Risk with Annual Mortality Rate of < 1% :
Low risk treadmill stress test
Normal or small myocardial perfusion defect at rest or with
stress
Normal stress echo wall motion or no change in a preexisting
limited resting wall motion on stress
Management of Chronic Stable Angina [5]
The management of chronic stable angina is mainly to relieve
symptoms and to prevent adverse events and complications.
Antiplatelet therapy with aspirin, clopidogrel, prasugrel or
ticagrelor is mandatory if there are no contraindications.
Even if the lipid levels are normal, lipid lowering drugs are
indicated in the management. By convention, the LDL-c is
targeted to below 70 mg / dL. Beta blockers are the mainstay
in the management of CSA and are ideally titrated to achieve a
resting heart rate of 60 bpm and an exercise heart rate of 75
bpm. Alternatively, calcium channel blockers like
diltiazem, verapamil or amlodipine may be used.
Angiotensin Converting Enzyme Inhibitors (ACEI) like Ramipril
(HOPE study) and Perindopril (EUROPA study) have been shown to
have salutary effects in CSA. For the relief of symptoms
and improving the quality of life, nitrates like
Nitroglycerine, Isosorbide mononitrate or Isosorbide dinitrate
are indicated though there are no studies to show that they
improve survival or prevent adverse events. Of late a new
drug, Ranolazine has been found beneficial in reducing the
symptoms of CSA especially when used in conjunction with beta
blockers or calcium channel blockers.
Acute coronary syndromes (ACS)
Acute coronary syndromes constitute Unstable angina pectoris,
ST elevation myocardial infarction (STEMI) and Non ST
elevation myocardial infarction (NSTEMI). All these are
medical emergencies and need to be treated in the acute
coronary care setting with either interventional or
non-interventional means. Often treatment in ACS is delayed
due to various factors and some of the factors are outlined
below.
The time for the patient to recognize the seriousness of the
problem and seek medical attention. Awareness of ACS is often
the most important factor in our setting. Most people do not
give importance to the symptoms especially when they are
atypical, thus losing precious time in the management of the
condition. Also there may be a bias between males and females
where the symptoms of a female with ACS are often underplayed
or ignored and hence females may seek medical help later than
males.
The other cause of delay may be the time taken for a pre
hospital evaluation, initial treatment or transportation of
the patient to a hospital. This may be due to various factors
like availability of Emergency medical services, lack of
adequate transportation facilities or delay in the
transportation due to traffic issues and other causes.
Once the patient is in the hospital, there may be a delay in
the diagnosis and initiation of treatment.
Finally, the time taken from the initiation of treatment to
the restoration of flow in the coronary artery determines the
outcome of treatment.
Delay can occur in any of these components and the shorter the
delay in getting the patient to the hospital and initiating
treatment, the better the prognosis and salvage of myocardium.
Reasons for delay - Patient related factors
Just as there are factors common to all causing a delay in the
treatment of patients, there are also factors related to
patients which are equally important in making timely help
available to patients with ACS.
Age is an important factor especially in our setting. Younger
patients seek medical help sooner than the elderly. A
breadwinner of the family gets to the hospital quickly even if
his symptoms are minor compared to an old dependent retiree.
Females are also slow in getting medical aid compared to
males. More so if they are unemployed homemakers. This has
been observed universally and is not confined to the
Asian population alone. In the West, it has been
observed that the black races seek aid later than the white
races. Also the socio economic status of the individual
counts. Patients belonging to the lower socio economic status
seek medical help later compared to those in the upper strata.
Other important factors noted are the low emotional or somatic
awareness of some individuals, or the presence of angina where
a prolonged pain is also dismissed as angina and timely
medical help is not sought. Patients with diabetes mellitus
who have atypical or no symptoms due to ACS also have a delay
in seeking help.
Risk stratification in ACS - TIMI Risk Score [6]
In acute coronary syndrome, stratification of risk is done
using the TIMI risk scoring which gives us an idea as to the
seriousness of the condition and the urgency of treatment.
There are seven criteria and each is given a score of one. It
was noted that when the score was 0 - 1, the risk was 4.7%,
for a score of 4 it was 19.9% and for a score of 6/7 it was
40.9% showing thereby that the risk exponentially increases
with the number of risk factors. The criteria for the risk
stratification are as follows:
1. Age > 65 years
2. Three or more coronary risk factors.
3. Known CAD - more than 50% stenosis
4. Current aspirin use
5. Two or more episodes of chest pain in the last 24 hours
6. Elevated cardiac biomarkers
7. ST elevation of 0.5 mm or more
Acute Coronary Syndromes - Treatment - Medical
The mainstay of treatment is the relief of symptoms and
restoration of coronary flow at the earliest. General measures
like monitoring in the intensive coronary unit, relief of
pain, oxygen inhalation, comfortable position and anxiolytics
are needed in all patients. A loading dose of aspirin 300 mg
and a loading dose of clopidogrel 300 mg are given immediately
on diagnosis. High dose atorvastatin - 40 - 80 mg is started.
Beta blockers are given intravenously or orally, if not
contraindicated. An infusion of nitroglycerine is helpful in
relieving pain and also controlling the blood pressure, if
elevated. It is also of help in reducing the pre load of the
left ventricle especially if there is evidence of LV
dysfunction. Angiotensin converting enzyme inhibitors and
angiotensin receptor blockers are of importance in those
patients with LV dysfunction. Intravenous heparin or low
molecular weight heparin is given after thrombolysis.
Thrombolysis in ACS - When and in Whom
[7]
Thrombolysis using a thrombolytic agent is considered in the
medical management on acute coronary syndrome in the setting
of STEMI only. In unstable angina and NSTEMI, thrombolysis is
contraindicated and appropriate interventional management is
considered. Thrombolysis is considered in patients who present
early especially within 3 hours of onset of symptoms and if
there is a delay in invasive management. The delay in
intervention could be due to the location of the patient or
the primary care center, transportation problems or a delay in
decision making by the patient or his relatives, as is common
in our set up.
In certain circumstances, the invasive strategy, though
indicated, is not possible and in them thrombolysis has to be
offered unless there is an absolute contraindication. A
cardiac catheterization laboratory may not be available
readily in some cases or the undue delay in reaching an
invasive set up. There may be prolonged transportation time
from the primary care center to an invasive cardiac facility
or there may be a patient or physician preference for invasive
versus noninvasive management. Also in cases where the door to
balloon time would take more than 1 hour, it is justified in
thrombolysing the patient. Patients with difficult vascular
access or those with low TIMI Risk scores may be subject to
thrombolysis rather than persist with invasive strategy.
Fibrinolytic Agents
The commonest fibrinolytic agent used is Streptokinase in a
dose of 1.5 million units given in 100 ml of normal saline
over 30 minutes. It is comparatively cheap and has been used
extensively and is rather predictable, though the vessel
patency after thrombolysis with streptokinase may be only
about 50%.
Tenecteplase is another thrombolytic agent which has the
advantage of being given as a single intravenous bolus dose.
It is given as 0.5 mg / kg as a single rapid bolus dose
and has the advantage of being ideal for pro-hospital
thrombolysis.
Reteplase in a dose of 10 units intravenously over a period of
two minutes followed by another 10 units after 30 minutes is
also available and used frequently. Alteplase is given in a
total dose of 100 mg.
Following thrombolysis the patient is given unfractionated
heparin- 60 units/kg bolus (upto 4000 units) followed by and
infusion of 14 units/kg/hour. Alternatively, low
molecular weight heparin like Enoxaparin may be given in two
doses of 0.4 to 0.6 ml subcutaneously daily.
NSTEMI - Management
The non invasive management of NSTEMI is mainly after
stratifying the risk. Invasive strategy is planned for
patients who need the same. Patients who cannot be taken for
invasive management due to the various reasons cited above are
decided on medical management. Thrombolysis is contraindicated
in NSTEMI. Other general measures, beta blockers,
antiplatelets, statins and heparin are given as in the
management of STEMI.
Addressing Co-morbidities and Complications
In addition to the noninvasive management of the cardiac
condition, stress is also given to the adequate management of
the co morbidities in patients with CAD. All risk factors
should be evaluated and appropriate advice given on their
management. Smoking should be strictly proscribed and obesity
is to be appropriately controlled with diet, exercise and
other measures. Diabetes mellitus which is one of the most
important co morbidities needs to be well controlled with
insulin during the acute phase and later with appropriate
drugs. Systemic hypertension needs to be controlled with
drugs, one or more as needed. Infections, especially
respiratory infection may be important co morbidity in most
patients and needs to be effectively addressed with
antibiotics dictated by microbiological studies. The presence
of left ventricular dysfunction or frank failure would
necessitate the use of diuretics in adequate doses and where
needed, assisted ventilation may have to be employed. Any fall
of blood pressure has to be treated with pressor agents after
ascertaining the cause for the hypotension. Any arrhythmias
noted during the acute phase have to be treated with the
appropriate anti arrhythmic drug.
In conclusion, the medical management of CAD assumes
importance in our prevailing conditions as the invasive
strategy is not available in all hospitals and due to the
logistical problems in patient transportation and accessing
medical facilities. Though in most patients, the invasive
strategy would be ideal given the proper circumstances, one
has to follow a middle path to identify the patients needing
urgent intervention and those that will benefit with medical
management alone.
References
1. Vamadevan SA and Dorairaj P. Coronary heart disease in
Indians: Implications of the INTERHEART study. Indian J Med
Res 2010, 132: 561-566.
2. McKeigue PM. Miller GJ, Marmot MG, Coronary heart disease
in South Asians: a review. Clin. Epidemiol 1989: 42: 579 -609.
3. Davies SW. Clinical presentation and diagnosis of coronary
artery disease: stable angina. British Medical Bulletin. 2001;
59: 17 -27.
4. Andrew C, David RH, Charanjit SR, Bernard JG. Chronic
Coronary artery disease: Diagnosis and management. Mayo Clin.
Proc. 2009; 84; 1130-1146.
5. Mathew P, Bradford TW, Kyle M, Ira MD. Medical Management
of Stable Coronary artery disease. Am. Fam. Physician.
2011; 83: 819 -826.
6. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T,
Papuchis G,. Mautner B, Corbalan R, Radley D, Braunwald E. The
TIMI Risk Score for Unstable angina / non- STEMI: A method for
prognostication and therapeutic decision making. JAMA
2000; 284: 835 -842.
7. Thomas JK, Bernard JG. Thrombolysis in Acute Myocardial
Infarction : Current Status. Med Clin N Am 2007 ; 9 :
617 -637.