CLINICIAN INTERVIEW

RECOGNIZING ACS AND

STRATIFYING RISK IN PRIMARY CARE

An interview with A. Michael Lincoff, MD, and Eric R. Bates, MD, FACC, FAHA

Dr Lincoff is an interventional cardiologist and the

Vice Chairman for Research at the Cleveland Clinic
Heart and Vascular Institute, and a Professor of Medicine
at the Cleveland Clinic Lerner College of Medicine of
Case Western Reserve University in Cleveland, Ohio. He
also serves as the Director of the Cleveland Clinic
Coordinating Center for Clinical Research (C5Research),
an organization devoted to clinical trials of new therapies
to address cardiovascular disease. Dr Lincoff received his
medical degree from Johns Hopkins University School of
Medicine, completed an internship and residency at Beth
Israel Deaconess Medical Center at the Harvard Medical
School in Boston, Massachusetts,, and received training in
cardiovascular medicine and interventional cardiology
through fellowships with the University of Michigan
Medical Center in Ann Arbor, Michigan, and the
Cleveland Clinic. He is board certified in internal medicine, cardiovascular disease, and interventional cardiology. Dr Lincoff s clinical and research interests include
coronary angioplasty and restenosis, acute coronary syndrome (ACS), acute myocardial infarction (MI), and the
development of new antithrombotic therapies for use during coronary intervention. Dr Lincoff has served as a
principal investigator for more than 15 clinical studies
that researched new therapies to treat acute MI, manage
unstable angina, or reduce complications of coronary
revascularization. He is a member of the Cardiovascular
and Renal Drugs Advisory Committee of the US Food
and Drug Administration, a Fellow in the American
College of Cardiology, and a Fellow in the European
Society of Cardiology.
Dr Bates is Professor of Internal Medicine at the
University of Michigan, Ann Arbor, specializing in cardiovascular disease. Dr Bates received his medical degree
from the University of Michigan Medical School and
completed his internship, residency, and fellowship in cardiology with the University of Michigan Health System.
He is board certified in internal medicine, cardiovascular

546

diseases, and interventional cardiology. Dr Bates serves as

the chair of the American College of Cardiology (ACC)
Ethics and Discipline Committee and is a member of the
ACC/American Heart Associations writing committee to
revise the 1999 guidelines for acute MI. He also serves as
a member of the American Board of Internal Medicine
Interventional Cardiology Test Committee. Dr Bates has
served on the steering committees of numerous multicenter clinical trials. His major clinical interests include
acute MI, ACS, and coronary artery disease. His research
time is devoted to the progress of fibrinolytic and catheterbased reperfusion therapy for acute MI and cardiogenic
shock, antiplatelet and anticoagulant therapy for coronary thrombosis, and coronary artery revascularization.
A senior clinical editor for Johns Hopkins Advanced
Studies in Medicine (JHASiM) interviewed Dr Lincoff
and Dr Bates to provide readers with insight into the current issues facing primary care physicians who encounter
patients at risk for ACS in daily practice.

JHASiM: Could you suggest any specific tools or

strategies for primary care physicians (PCP) to best
identify patients who are at risk for acute coronary
syndrome (ACS) and require additional follow-up?
Dr Bates: The first thing that PCPs should begin
with is a review of the patients medical history. It is
also important to emphasize the potential difference in
symptoms and diagnosis based on specific demographic factors, such as the patients gender or socioeconomic background. Differential diagnosis is critical,
because chest pain could be consistent with approximately 20 different diagnoses, with possible causative
factors varying from acid reflux, the flu, or depression

Vol. 7, No. 17

December 2007

CLINICIAN INTERVIEW

to pulmonary embolism, to name a few. PCPs should

be comfortable taking a chest pain history and differentiating ischemic chest discomfort from nonischemic
chest discomfort in routine practice.
Dr Lincoff: When patients are seen in the emergency department (ED) or urgent care settingor in
the office setting, for that matterclinicians should
first assess the likelihood that the patient has coronary
disease and whether the pain that they are experiencing is consistent with coronary or noncoronary chest
pain. Symptoms on exertion in particular would be
consistent with coronary chest pain, especially if
accompanied by other symptoms, such as fatigue or
shortness of breath. Chest pain that is nonischemic in
nature would more likely be associated with pain that
is reproduced by pressing on the chest or chest pain
that occurs on rest but not exertion. On the other
hand, exertional chest pain that has progressed to pain
at rest is worrisome and consistent with ischemia. Also,
chest pain in patients with a history of coronary disease, diabetes, or vascular disease should be highly suspect as ischemic pain.
JHASiM: If a patient does present with suspected
ischemia, how should clinicians proceed with follow-up in the office setting?
Dr Bates: An electrocardiogram (ECG) would be
the most important next step in evaluating the patient,
and most clinicians have the ability to perform an ECG
in their office. Also, clinicians should consider blood
testing for important biomarkers, including troponin,
creatinine kinase MB, and brain natriuretic peptide
as well as glucose, electrolytes, creatinine, low-density
lipoprotein cholesterol, and white blood cell countto
further support or rule out an ischemia diagnosis.
Dr Lincoff: Careful examination is also important.
For example, if the initial examination reveals signs of
other cardiac conditions, such as heart failure or
arrhythmia, this indicates that ischemia is more likely
the cause of symptoms and that the patient may be at
high risk for complications. Also, a normal ECG would
not necessarily rule out ischemia, but a markedly abnormal ECG could support a diagnosis of ischemia. A
physical examination and ECG are insensitive in detecting ischemia, but both are relatively specific when findings are abnormal. Going back to medical history, we
should still stress the importance of traditional risk factors. The available research suggests that up to 80% of
the predictive value for the development of atheroscle-

Johns Hopkins Advanced Studies in Medicine

PRACTICE RECOMMENDATIONS

FOR

ACS

The ACC/AHA guidelines for the management of

UA/NSTEMI emphasize that primary care physicians
should evaluate all patients for major cardiovascular
risk factors at intervals of 3 to 5 years. Those with suspected ischemic pain should not be evaluated over the
phone, but should be immediately referred to a facility with the ability to administer a 12-lead ECG to
arrive at a more accurate diagnosis. Early risk stratification is also recommended in all patients presenting
with suspected ACS. Patients with suspected ACS,
despite normal ECG or biomarkers, should be
referred for follow-up evaluations that include a repeat
ECG, repeat biomarkers analysis, and stress test to
provoke ischemia. Low-risk patients referred for outpatient stress testing should receive precautionary
aspirin, sublingual nitroglycerin, and a blocker while
awaiting results of the stress test. Patients with definite
ACS who experience ongoing ischemia, positive biomarkers, ST-segment elevations or deep T-wave inversions on ECG, hemodynamic abnormalities, or a
positive stress test should be admitted to the hospital
setting for further management.
Source:
Anderson JL, Adams CD, Antman EM, et al.
J Am Coll Cardiol. 2007;50:e1-e157.
Web site:
http://content.onlinejacc.org/cgi/reprint/50/7/e1
Strength of Evidence:
A panel of experts in the prevention, detection, and
management of cardiovascular disease developed the
ACC/AHA guidelines for the management of
UA/NSTEMI. The recommendations for UA/NSTEMI discussed above are all Class I recommendations
that have a high potential for benefit and low potential for risk based on the available clinical evidence.

rotic heart disease is linked to major traditional risk factors, including diabetes, hypertension, dyslipidemia,
smoking, and a family history of heart disease.
JHASiM: In patients who do present in primary
care with ACS, which medications should be prescribed prior to further care in the hospital setting?
Dr Bates: This may seem obvious, but it is still critical to emphasize the importance of aspirin in patients

547

CLINICIAN INTERVIEW

with suspected or established coronary disease. Some

patients with established disease neglect to continue
on aspirin, thinking that their more expensive prescription medications are sufficient to protect against
future events. Aspirin is the most important intervention that we have, and it should be routinely used in
these patients. Sublingual nitroglycerin and a blocker also are warranted.
Dr Lincoff: For a patient in whom an ACS seems
likely, early administration of clopidogrel is recommended. This is still a point of some contention, as
cardiac surgeons may be reluctant to operate for several days after a clopidogrel loading dose because of concerns regarding excess bleeding. In most cases, though,
the likelihood that a patient presenting to primary care
would require urgent surgical intervention is low,
therefore, clopidogrel is probably safe in these patients.
Also, there have been limited data to suggest that acute
treatment with a statin may improve outcomes in
patients with ACS undergoing percutaneous coronary
intervention (PCI) because of immediate stabilization
of the plaque with the statin.

PCPs should be aware of the most recent American

College of Cardiology/American Heart Association
guidelines for the evaluation and management of
patients with suspected ACS (Figure),1 thus they are
aware of the best practices governing the care of these
patients from diagnosis through hospital discharge.
Dr Lincoff: Because ACS encompasses both
STEMI and NSTEMI, the primary strategy should
be a prompt ECG to arrive at the most likely diagnosis, certainly within 10 minutes of arrival with
chest pain. Most facilities have a protocol to deliver
prompt PCI, within 90 minutes or less, if the patient
is diagnosed with STEMI. Prompt PCI in STEMI
has been adopted as a quality-of-care indicator for
many healthcare payers, including Medicare, therefore hospitals are highly motivated to improve these
times. Strategies, such as having ED physicians activate the catheterization laboratory, requiring interventional staff to arrive within 30 minutes of paging,
and having emergency medical services staff transmit
ECGs before hospital arrival, have all improved the
time from presentation to PCI.

JHASiM: Could you describe the most important

features of any standard algorithms or care pathways to improve early recognition of ACS?
Dr Bates: The most important aspects of protocols
and care pathways emphasize prompt care. First of all,
many pathways now require that patients presenting
with chest pain are seen and treated within 30 minutes
of arrival. The majority of protocols also stress that
patients with chest pain should receive an ECG within 10 minutes of arrival and that a physician should
promptly evaluate the findings. Under new care pathways, the ED is now often responsible for delivering
essential medications, such as aspirin, clopidogrel,
unfractionated heparin or enoxaparin, nitroglycerin,
and perhaps blockers. In ST-segment elevation
myocardial infarction (STEMI), these medications
prepare the patient for prompt PCI.
In nonST-segment elevation myocardial infarction (NSTEMI), these medications stabilize the
patient and prepare the patient for later intervention if
the clinician determines that the patient is at high risk
of ischemic complications. It is also important to note
a third pathway into which the bulk of patients may
fall, in which they are admitted overnight to receive
further diagnostics, including blood tests, repeat
ECGs, and a stress test, to rule out ACS. In general,

JHASiM: Could you discuss some risk stratification

tools used in ACS?
Dr Bates: The Thrombolysis in Myocardial
Infarction (TIMI) risk score (Table)2 and the Global
Registry of Acute Coronary Events (GRACE) risk calculator3 are both useful guides for risk stratification
and highlight factors that are easy to track in daily
practice. After taking a medical history, performing a
physical examination and an ECG, and ordering blood
testing for biomarkers, risk stratification would be an
important addition to providing a comprehensive evaluation in patients with suspected ACS.

548

JHASiM: Does ACS care vary substantially by hospital? If so, should PCPs be aware of these differences and direct their patients accordingly?
Dr Lincoff: I think that one of the advantages of
having protocol-driven management in ACS is that
the care delivered should be independent of the
physicians specialty. Patients who have a fairly high
likelihood of ACS should be managed with either
prewritten orders or a treatment protocol that stresses the use of aspirin, clopidogrel, blockers, and an
antithrombotic (eg, heparin, low-molecular-weight
heparin, bivalirudin, or fondaparinux), as well as a
glycoprotein IIb/IIIa inhibitor in some patients. The

Vol. 7, No. 17

December 2007

CLINICIAN INTERVIEW

Figure. ACC/AHA Guidelines Algorithm for the Evaluation and Management of Patients with Suspected ACS

To facilitate interpretation of this algorithm and a more detailed discussion in the text, each box is assigned a letter code that reflects its level in the algorithm and a number that is allocated from left to right across the diagram on a given level.
ACC/AHA = American College of Cardiology/American Heart Association; ACS = acute coronary syndrome; ECG = electrocardiogram; LV = left ventricular.
Reprinted with permission from Anderson et al. J Am Coll Cardiol. 2007;50:e1-e157.1

protocol should emphasize correct dosing, as dosing

errors have been associated with a higher risk of
bleeding events and poor outcomes. Often, clinicians
do not take underlying comorbidities into account
that could affect dosing requirements. Clinicians
should be particularly alert to the fact that mild renal
insufficiency is common in older patients, which
could impact their ability to metabolize these drugs
and confer a higher bleeding risk.
Dr Bates: Although capabilities differ between hospitals, there should be a standard of care across all
health systems to deliver basic evidence-based services,
including risk stratification and proper medical support, to all patients diagnosed with ACS.

Johns Hopkins Advanced Studies in Medicine

JHASiM: How do facilities that do not have PCI

capabilities coordinate with other specialty centers to provide prompt care for patients requiring
intervention?
Dr Lincoff: Many hospitals without PCI capability establish hub-and-spoke relationships with centers that perform coronary interventional
procedures, allowing for expedited transfer. This
works well from both perspectives, because the
receiving hospital knows how the patient was managed before arrival, and the referring hospital has an
established protocol of one center to which high-risk
patients are sent. This could apply to patients with
STEMI and high-risk patients with NSTEMI, such

549

CLINICIAN INTERVIEW

as those with ongoing chest discomfort, arrhythmia,

or heart failure.
Dr Bates: Again, the ability to stratify patients by
risk in primary care, with tools such as the TIMI risk
score and GRACE risk calculator, is critical so that
high-risk individuals are promptly referred to centers
with PCI capability, when possible.

Table.The TIMI Risk Score for Patients with

NonST-Elevation ACS
A. Scoring System
Points
Patient History
Age 65 y
3 risk factors for CAD (history, hypertension,
hypercholesterolemia, overweight/obesity, and
current smoker)
Known CAD (stenosis 50%)
Aspirin use in the past 7 d
Clinical Presentation
Recent (24 h) severe angina
Elevated cardiac markers
ST deviation of 0.5 mm on ECG

1
1

1
1
1
1
1

B. Risk of Cardiac Events (%) by TIMI Score*

Score

Risk of All-Cause
Mortality or MI

Risk of All-Cause Mortality, MI, or

Urgent Revascularization

0/1
2
3
4
5
6/7

3
3
5
7
12
19

5
8
13
20
26
41

*Based on the TIMI 11b trial.

ACS = acute coronary syndrome; CAD = coronary artery disease; ECG =
electrocardiogram; MI = myocardial infarction; TIMI = Thrombolysis in
Myocardial Infarction.
Adapted with permission from Antman et al. JAMA. 2000;284:835-842.2

550

JHASiM: What are the major points that should be

communicated to the PCP who is likely to see
patients at risk for ACS in daily practice?
Dr Lincoff: The key messages can be summed up in 4
major points. First of all, patients should be properly
assessed to determine the likelihood that symptoms are a
result of cardiac disease. If it is suspected cardiac disease,
then an initial discrimination between STEMI (high
risk) or NSTEMI (lower risk) should be made so that the
individual receives prompt care. Once a patient is triaged
to the appropriate treatment center, initial medical care
should be delivered according to a standard protocol.
Finally, patients with STEMI or high-risk NSTEMI
should receive prompt intervention with PCI.
Dr Bates: The importance of aspirin in patients
with suspected ACS, as well as those with established
coronary disease, should be emphasized again. Even if
a patient does not seem to be in immediate danger,
those presenting with suspicious chest pain should also
be referred for a stress test, either immediately or within the period of 1 or 2 days.

REFERENCES
1. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA
2007 guidelines for the management of patients with unstable angina/nonST-elevation myocardial infarction: a report
of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing
Committee to Revise the 2002 Guidelines for the
Management of Patients With Unstable Angina/NonSTElevation Myocardial Infarction) developed in collaboration
with the American College of Emergency Physicians, the
Society for Cardiovascular Angiography and Interventions,
and the Society of Thoracic Surgeons endorsed by the
American Association of Cardiovascular and Pulmonary
Rehabilitation and the Society for Academic Emergency
Medicine. J Am Coll Cardiol. 2007;50:e1-e157.
2. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score
for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA.
2000;284:835-842.
3. Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of
hospital mortality in the global registry of acute coronary
events. Arch Intern Med. 2003;163:2345-2353.

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December 2007