Clinical Review & Education

JAMA Internal Medicine | Special Communication | LESS IS MORE

Eliminating Creatine Kinase–Myocardial Band Testing
in Suspected Acute Coronary Syndrome
A Value-Based Quality Improvement
Matthew D. Alvin, MD, MBA, MS, MA; Allan S. Jaffe, MD; Roy C. Ziegelstein, MD, MACP; Jeffrey C. Trost, MD

Author Audio Interview
Cardiac biomarker testing is estimated to occur in nearly 30 million emergency department
visits nationwide each year in the United States. The American College of Cardiology/
European Society of Cardiology indicate that cardiac troponin is the biomarker of choice
owing to its nearly absolute myocardial tissue specificity and high clinical sensitivity for
myocardial injury. Multiple academic medical centers have implemented interventions to
eliminate the routine ordering of creatine kinase–myocardial band tests, with published
patient safety outcomes data; however, creatine kinase–myocardial band testing is still
Author Affiliations: Author
ordered in many hospitals and emergency departments. Eliminating a simple laboratory test affiliations are listed at the end of this
that provides no incremental value to patient care can lead to millions of health care dollars article.
saved without adversely affecting patient care quality, and in this case potentially improving Corresponding Author: Jeffrey C.
patient care. Trost, MD, Division of Cardiology,
Department of Medicine, Johns
Hopkins University School of
JAMA Intern Med. doi:10.1001/jamainternmed.2017.3597 Medicine, 301 Mason F. Lord Bldg,
Published online August 14, 2017. Baltimore, MD 21224
(jtrost2@jhmi.edu).

A
cute coronary syndrome (ACS) is one of the leading causes annually. Not included in these estimates are additional unneces-
of mortality in the United States. Since the 2000 Ameri- sary expenditure and potential harm associated with subsequent
can College of Cardiology (ACC)/European Society of noninvasive and invasive testing that may result from false-
Cardiology (ESC) redefinition of acute myocardial infarction positive results.
(AMI), which was revised into the 2007 and 2012 Universal Defi- Once the cornerstone of AMI diagnosis, CK-MB has not yet been
nition of AMI, cardiac troponin (cTn) has been the biomarker of eliminated from practice despite considerable evidence support-
choice owing to its nearly absolute myocardial tissue specificity ing cTn as the preferred biomarker.8,11 Data published after distri-
and high clinical sensitivity for myocardial injury.1,2 Cardiac tro- bution of the ACC/ESC/AHA3-5 recommendations show the these
ponin is preferred by both clinical (ACC/ESC/American Heart clinical practice guidelines have not succeeded in refining practice.
Association [AHA]) 3-5 and biochemical (National Academy of Specifically, CK-MB is still used in many US clinical pathology
Clinical Biochemistry)6,7 guideline groups, for similar reasons. In laboratories and US EDs.12,13 Based on the College of American Pa-
the most recent universal definition of AMI, creatine kinase- thologists proficiency survey in 2013, 1558 of 1995 national US
myocardial band (CK-MB) is described as an alternative to be used laboratories (77%) still use CK-MB.12 In 2009, Parker and Suter13 sur-
only if cTn is not available.2 The 2014 AHA/ACC guidelines con- veyed 98 ED physician leaders in 21 academic and 77 community
clude that CK-MB provides no additional value for diagnosing AMI EDs regarding the use of cardiac biomarkers and found that 77%
(class III, level of evidence A).5 (76 of 98) still use CK-MB. Collinson et al14 found that of the nearly
The ideal biomarker test for the diagnosis of AMI should be 40% of North American and European laboratories (n = 533) offer-
highly sensitive and specific, rapidly obtained and analyzed, and ing CK-MB testing in 2006, 25% continued to offer the test even af-
lead to treatment decisions that provide high value, in terms of ter the national guidelines discussed above recommended against
clinical benefit relative to cost.8 The importance of this goal stems its use. Cappelletti et al15 added to the findings by Collinson et al14
from the sheer number of patients receiving cardiac biomarker by adding data from Italy (n = 126 laboratories) that showed 20.2%
testing and the resulting contribution to health care expenditure of laboratories continue to use CK-MB.
in the United States each year. In 2010, Makam and Nguyen9 This retention of CK-MB has been attributed to clinicians’ re-
showed via the National Hospital Ambulatory Medical Care Sur- luctance to rely on cTn in certain clinical situations, as well as clini-
vey (n = 44 448 emergency department [ED] visits) that cardiac cian familiarity.8,11 In 2010, a study coauthored by 7 large academic
biomarker testing (both cTn and CK-MB) occurred in 16.9% of all medical centers labeled CK-MB as 1 of 10 tests that no longer pro-
visits to the ED. The authors extrapolated this to represent 28.6 vide value,16 and a growing number of medical centers have aban-
million ED visits nationwide. Considering Medicare’s 2016 Clinical doned use of CK-MB.8 With the goal of advancing high value prac-
Diagnostic Laboratory Fee Schedule 1 0 (national payment tice, as defined by the ACC, ESC, AHA3-5 and National Academy of
amounts for cTn and CK-MB of $13.40 and $15.73, respectively), Clinical Biochemistry, this implementation guideline is designed to
approximately $416 million is spent on cardiac biomarker testing assist institutions in eliminating unnecessary CK-MB testing.

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Clinical Review & Education Special Communication Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS

post-PCI myocardial injury is not an important clinical end point.39
Evidence-Based Guidelines: Even if clinicians decide to assess cardiac biomarkers in this setting,
Troponin and CK-MB Tests post-PCI cTn and CK-MB values provide equally accurate prognos-
tic information.39 Because this guideline is focused on cardiac bio-
NumerousstudieshavecomparedCK-MBandcTnwithrespecttotheir marker use in routine ACS diagnosis, rather than cardiac biomarker
diagnostic precision related to the initial diagnosis of AMI, the assess- use following PCI, we defer further discussion and/or recommen-
ment of reinfarction, and prognosis after major cardiovascular events. dation with respect to this ongoing clinical controversy.
Cardiac troponin has been shown to be highly sensitive for AMI Another potential area of controversy concerns the appropri-
(99.2%)17 and to be more specific than CK-MB (lower false-positive ate use of cTn in clinical practice.40 The major strength of using
rate) owing to its exclusivity in cardiac myocytes (vs CK-MB, which may cTn—its specificity for cardiac injury—is also a potential shortcom-
be elevated with skeletal muscle damage).16-19 Hawkins et al20 cal- ing, because cTn detects myocardial injury irrespective of the spe-
culated a specificity of cTn testing as high as 92% compared with 40% cific cause. Consequently, many noncardiac conditions associated
for CK-MB. Lin et al21 observed that among patients with suspected with secondary myocardial injury, such as pulmonary embolus, se-
AMI who also had negative cTn results, approximately 10% of pa- vere anemia, and severe hypotension from any cause, are associ-
tients had abnormally high CK-MB.22 Similarly, Antman et al23 evalu- ated with abnormal cTn. Wilson et al40 reported a high prevalence
ated cardiac biomarker levels in patients with ACS symptoms and of elevated cTn in a large group of hospitalized patients due to non-
found that 238 of 948 patients (25%) initially classified as having un- cardiac conditions and has suggested that this may represent an ex-
stable angina owing to normal CK-MB tests actually had elevated cTn ample of overuse of cTn. Another group has reported a small series
levels. Thus, the use of CK-MB may potentially misclassify individu- of patients in which the quantity of troponins ordered per patient
als with ACS by mistakenly diagnosing unstable angina in some pa- exceeded guideline recommendations.41 We acknowledge that the
tients with true myocardial infarction. real-world use of cTn, with respect to appropriate clinical indica-
In patients with chronic renal disease, the diagnosis of ACS can tion and quantity over time, deserves further study and quality im-
be challenging, as cTn levels may be chronically elevated. However, provement initiatives designed to refine usage.
CK-MB has been shown to provide no incremental value over cTn in Finally, Saenger et al8 have observed that concomitant use of
the diagnosis of ACS in patients with chronic renal disease.24,25 In CK-MB and cTn is often confusing for physicians, and they are aware
fact, CK-MB levels are often elevated in patients on dialysis in the of situations in which such confusion has negatively affected pa-
absence of ACS signs and/or symptoms.25 tient care. An example of a potentially confusing clinical situation is
In terms of time to diagnosis, both CK-MB and troponin are when a patient is admitted with possible symptoms of ACS and is
equally rapid in ACS diagnosis,8 but with more sensitive assays, cTn found to have an abnormally elevated CK-MB levels in the setting
rises much more rapidly.26-28 In addition to its superior sensitivity of sequentially normal troponin levels. Although normal sequen-
and specificity, cTn yields stronger prognostic information. In pa- tial troponin values exclude the diagnosis of acute myocardial
tients with ACS, the CRUSADE investigators (n = 29 357)29 showed injury—and are associated with a favorable short-term prognosis
that elevated cTn is associated with in-hospital mortality, regard- regardless of the CK-MB levels—some physicians might errone-
less of CK-MB levels. However, when CK-MB levels are elevated in ously conclude that the patient has suffered acute myocardial
the presence of a normal cTn, in-hospital mortality is comparable to injury due to CK-MB elevation. Others might wonder if there is
CK-MB levels and cTn both being negative.29-31 Most important, those another condition (ie, skeletal muscle breakdown) responsible for
with elevated CK-MB values but normal cTn levels do not manifest the CK-MB elevation and might erroneously devalue the impor-
an adverse prognosis.29-31 tance of the patient’s symptoms and electrocardiogram in making
Despite a longstanding, commonly held physician belief that the diagnosis of ACS.42 We would argue that elimination of rou-
CK-MB is more useful than cTn for detecting reinfarction, no study tine CK-MB ordering is not only high value because it offers no
has shown that CK-MB levels are superior to cTn in this regard.32,33 benefit and results in considerable cost but also because elimina-
Indeed, most data confirm that cTn provides far better estimates be- tion of CK-MB may reduce physician confusion, improve under-
cause it is less impacted by changes in the amount of marker re- standing of the proper use of cTn, and consequently reduce
leased with reperfusion.34 Single values correlate closely with in- potential patient harm.
farct size as determined by cardiac magnetic resonance imaging.35
Apple et al36 showed that both biomarker levels rise similarly with
reinfarction. The most recent ACC/AHA/ESC guidelines support the
use of cTn over CK-MB for diagnosing reinfarction.3-5
Safety and Quality Outcomes Data:
Most patients with ACS are treated with either surgical or per- Eliminating CK-MB Testing
cutaneous revascularization.37,38 The use of CK-MB or cTn follow- Multiple academic medical centers have implemented interventions
ing percutaneous coronary intervention (PCI) is controversial, as to eliminate the routine ordering of CK-MB and measured associ-
there is no current consensus regarding the definition, prognosis, ated cost savings and impact on patient safety (Table).12,43-46
and subsequent treatment of periprocedural myocardial infarction Larochelle et al44 recorded data on patients with suspected ACS
diagnosed by cardiac biomarker elevation alone. Some groups have (n = 60 494 patients preintervention; n = 24 341 patients postinter-
suggested that CK-MB is superior to cTn in terms of detecting peri- vention) over a period of 43 months (31 months preintervention; 12
procedural myocardial infarction,38 while others have argued that months postintervention). They initially developed an institutional
post-PCI cardiac biomarkers are not useful because prognosis is re- guideline in collaboration with cardiologists to specify appropriate or-
lated to the pre-PCI cTn value, and when that is taken into account, dering of cardiac biomarkers for the diagnosis of AMI. The guideline

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Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS Special Communication Clinical Review & Education

Table. Trials Eliminating CK-MB Testing

Source No. Duration Intervention Results
Baron et al,43 2012 Not specified 4 mo Implemented BPA in the CPOE 87% reduction in CK-MB tests
system when physicians (n = 1106 to 139/mo)
searched for CK-MB, tracked Fewer orders after searches for
searches/Orders by provider CK-MB testing
Restricted CK-MB testing to Fewer searches for CK-MB testing
patients who were post-PCI Physicians who had not seen the
and postcardiac surgery BPA (0 prior searches) were more
likely (P < .01) to place a search
Larochelle et al,44 2014 84 835 12 mo Developed institutional 95% reduction in CK-MB tests
guideline in consultation with with $720 000 in annual savings
cardiologists to order No decrease in ACS incidence
troponin alone in patients
with suspected ACS
Conducted educational
sessions with IM and ED
physcians
Disseminated a pocket-size
guideline reference card
Removed CK-MB from CPOE
ACS routine order sets and
created BPA when physicians
attempted to order CK-MB
tests
Singh and Baweja,12 2014 37 418 6y Removed CK-MB testing from 99.8% reduction in CK-MB tests
CPOE ACS routine order sets (12 057 in 2007, 36 in 2013)
Reviewed cases (n = 171) No CK-MB test for the 171
where CK-MB tests were still patients provided diagnostic or
ordered prognostic value
Le et al,45 2015 14 571 12 mo Removed CK-MB testing from 80% reduction in CK-MB tests
CPOE ACS routine order sets with $47 286 in annual savings
No missed diagnosis of ACS
Sullivan et al,46 2016 Not specified 12 mo Removed CK-MB testing from
84% reduction in CK-MB tests
CPOE ACS routine order sets
(43.7 to 6.8 tests per day)
Costs decreased from $546 per
day to $85 per day, $168 000
annual savings
No adverse effects on mortality
Abbreviations: ACS, acute coronary syndrome BPA, best practice alert; CK-MB, creatine kinase–myocardial band; CPOE, computerized provider order entry;
ED, emergency department; IM, internal medicine; PCI, percutaneous intervention.

tient (95% CI, −1.00 to −0.92). The authors estimated a 95% reduc-
Figure 1. Best Practice Alert Example
tion in CK-MB tests, translating to $720 000 in annual savings.
Best Practice Alert – CK-MB Lab Test Similarly, Baron et al43 removed CK-MB from routine order sets
and implemented a BPA into their CPOE system without additional
Based on national evidence-based guidelines1,2,3:
- Troponin is the preferred marker in diagnosing AMI/ACS educational sessions. After only 2 months postimplementation, they
- CK-MB in addition to troponin adds no incremental diagnostic value
noted an 87% decrease in CK-MB orders. In addition, they noted
1. Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update
incorporated into the ACCF/AHA 2007 guidelines for the management of patients with
fewer orders after searches and fewer searches for CK-MB over this
unstable angina/non-ST-elevation MI. J Am Coll Cardiol. 2013; 61:e179-e347.
2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the
time, arguing for a long-term educational benefit for the BPA. Mul-
Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of tiple other groups, including Mayo Clinic, simply removed CK-MB
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. J Am Coll Cardiol. 2014; 64:e139-228. from routine order sets and found 80.0% to 99.8% reductions in
3. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the
management of ST elevation MI. J. Am Coll Cardiol. 2013; 61:e78-e140. CK-MB orders with significant cost savings and without negative im-
pact on patient care or missed AMI diagnoses.8,12,43-46
An example of a Best Practice Alert to appear in the physician ordering system
when attempting to order a creatine kinase–myocardial band.

Implementation Blueprint:
advised practitioners to order cTn alone, without CK-MB. The au-
Eliminating CK-MB Testing
thors then implemented multiple interventions, including educa-
tional sessions for internal medicine and ED physicians, dissemina- With clear evidence to support elimination of CK-MB from clinical
tion of pocket-sized quick reference cards with the recommended care for the diagnosis of ACS and based on experience eliminating
ordering algorithm, and removal of CK-MB from ACS routine order sets CK-MB at our respective institutions, we devised a blueprint for other
within the computerized provider order entry (CPOE) system. A Best institutions to use in enacting quality improvement initiatives. The
Practice Advisory (BPA) was created in the CPOE system using the in- methodology and theory of the blueprint and quality improve-
stitutional guideline to alert physicians who attempted to order CK- ment initiative are based on the US Health Resources and Services
MB. Physicians could, if desired, order CK-MB manually. By 12 months Administration strategies for developing and implementing a qual-
postintervention, the estimated number of CK-MB tests per patient ity improvement initiative, with a focus on education, action, and
was 0, representing an absolute change of −0.96 CK-MB tests per pa- measurement of results.47 The leader of each institution should

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Clinical Review & Education Special Communication Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS

2. Partner with information technology and/or laboratory medi-
Figure 2. Pocket Card
cine staff to remove CK-MB from standardized ACS routine
High Value Practice Academic Alliance Pocket Card order sets. Doing this simple step alone has been shown to sig-
Cardiac Biomarker Ordering for ACS/AMI nificantly reduce CK-MB ordering (Table).8,12,45,46
Obtain troponin you suspect Acute Coronary Syndrome (ACS)/Acute Myocardial Infarction (AMI)
3. Partner with information technology and/or laboratory medi-
Initial presentation cine staff to create and integrate a best practice alert into the
6-9 hours later
CPOE to appear when clinicians order CK-MB, such as:
• According to national guidelines, troponin is the preferred bio-
12-24 hours later intermediate to high clinical suspicion and/or recurrence of
symptoms marker for detecting myocardial injury; CK-MB is only appro-
STOP CHECKING. If troponin is abnormal: priate if troponin testing is unavailable. Figure 1 provides an
• correlate with clinical presentation to determine likihood of ACS
• there is no utility to trending abnormal troponin to peak or resolution
example.43,44
• patient has ACS, there is clinical concern for reinfarction, additional 4. Measure data preintervention and postintervention (efficacy
troponin measurements may be useful

CK-MB in addition to troponin offers no incremental diagnostic value.
points).
• Number of cTn and CK-MB tests ordered, including stratifica-
tion by department and patient setting (ED, inpatient, medi-
cine vs nonmedicine units, ICU vs non-ICU).
• Incidence, missed diagnoses, and mortality of AMI to ensure pa-
tient safety.
An example of a pocket card for mass distribution to faculty and house staff
regarding creatine kinase–myocardial band and troponin testing. • Review cases where CK-MB is still ordered to determine if it
provides value.
assess applicability of this blueprint based on the CK-MB ordering • If necessary, track usage by physician to develop performance
frequency at their respective institution. feedback profiles.
1. Design and implement a hospital-wide educational campaign. • Calculate reduction in charges to patients and health plans, as
• Prior to implementation, it is important for health care leaders well as any decrease in hospital costs.
to establish sufficient organizational readiness for change, spe- Though seemingly straightforward to articulate, we acknowl-
cifically in conjunction with these stakeholders, whose order- edge that significant barriers to implementation exist, and in this case
ing practices will be affected by such changes. Tools to mea- the biggest hurdle has been convincing physicians who have or-
sure readiness for change have been previously studied and may dered CK-MB for years to change their practice. Successful deimple-
be used.48,49 mentation of CK-MB requires leadership support, education, and re-
• Collaborate with physician representatives from the departments assurance that diagnostic efficacy will not be compromised. Other
of cardiology, internal medicine, and emergency medicine. Front- challenges relate to manpower as well as modifications and data col-
line physicians in these departments order the majority of car- lection from the electronic medical record. To optimize manpower,
diac biomarkers within most health care institutions and are the academic centers can engage house staff because this will also
primary stakeholders in the current system of care for ACS ensure longstanding change. Again, leadership commitment to al-
patients. locating information technology resources for data collection and
• Academic institutions must engage the house staff as members clinical decision support tools is critical.
of the quality improvement team for an effective initiative.
• Collaborate with secondary stakeholders, such as pathology
and/or laboratory staff, to acquire insight and advice on these
Conclusions
changes.
• Inform physicians that CK-MB adds to the health care system Creatine kinase–myocardial band testing provides no incremental
financial burden without adding value to patient care. value to patient care, and its elimination can lead to millions of health
• Present the evidence supporting elimination of CK-MB and ex- care dollars saved without adversely affecting patient care. This is
clusive use of cTn to diagnose AMI, identify reinfarction, and es- backed by both strong evidence-based guidelines and experiences
timate infarct size. Education may be provided through vari- from multiple institutions. The blueprint presented here should be
ous venues, including lectures, pocket cards (Figure 2), online carefully considered by health care leaders and clinicians as the first
modules, social media demonstrations, and simulations.44 step to finally putting the CK-MB laboratory test to rest.

ARTICLE INFORMATION Department of Medicine, Johns Hopkins Bayview collaborating on quality improvement, research,
Accepted for Publication: June 12, 2017. Medical Center, Baltimore, Maryland (Ziegelstein, and education related to high-value healthcare.
Trost).
Published Online: August 14, 2017. REFERENCES
doi:10.1001/jamainternmed.2017.3597 Conflict of Interest Disclosures: None reported.
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Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS Special Communication Clinical Review & Education

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