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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

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 ordered in many hospitals and emergency departments. Eliminating a simple laboratory test that provides no incremental value to patient care can lead to millions of health care dollars saved without adversely affecting patient care quality, and in this case potentially improving patient care.

JAMA Intern Med. doi:10.1001/jamainternmed.2017.3597 Published online August 14, 2017.

Published online August 14, 2017. Author Audio Interview Author Affiliations: Author

Author Affiliations: Author affiliations are listed at the end of this article.

Corresponding Author: Jeffrey C.

Trost, MD, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 301 Mason F. Lord Bldg, Baltimore, MD 21224

A cute coronary syndrome (ACS) is one of the leading causes

of mortality in the United States. Since the 2000 Ameri-

can College of Cardiology (ACC)/European Society of

Cardiology (ESC) redefinition of acute myocardial infarction (AMI), which was revised into the 2007 and 2012 Universal Defi- nition of AMI, cardiac troponin (cTn) has been the biomarker of choice owing to its nearly absolute myocardial tissue specificity and high clinical sensitivity for myocardial injury. 1,2 Cardiac tro- ponin is preferred by both clinical (ACC/ESC/American Heart Association [AHA]) 3-5 and biochemical (National Academy of Clinical Biochemistry) 6,7 guideline groups, for similar reasons. In the most recent universal definition of AMI, creatine kinase- myocardial band (CK-MB) is described as an alternative to be used only if cTn is not available. 2 The 2014 AHA/ACC guidelines con- clude that CK-MB provides no additional value for diagnosing AMI (class III, level of evidence A). 5 The ideal biomarker test for the diagnosis of AMI should be highly sensitive and specific, rapidly obtained and analyzed, and lead to treatment decisions that provide high value, in terms of clinical benefit relative to cost. 8 The importance of this goal stems from the sheer number of patients receiving cardiac biomarker testing and the resulting contribution to health care expenditure in the United States each year. In 2010, Makam and Nguyen 9 showed via the National Hospital Ambulatory Medical Care Sur- vey (n = 44 448 emergency department [ED] visits) that cardiac biomarker testing (both cTn and CK-MB) occurred in 16.9% of all visits to the ED. The authors extrapolated this to represent 28.6 million ED visits nationwide. Considering Medicare’s 2016 Clinical Diagnostic Laboratory Fee Schedule 10 (national payment amounts for cTn and CK-MB of $13.40 and $15.73, respectively), approximately $416 million is spent on cardiac biomarker testing

annually. Not included in these estimates are additional unneces- sary expenditure and potential harm associated with subsequent noninvasive and invasive testing that may result from false- positive results. Once the cornerstone of AMI diagnosis, CK-MB has not yet been eliminated from practice despite considerable evidence support- ing cTn as the preferred biomarker. 8,11 Data published after distri- bution of the ACC/ESC/AHA 3-5 recommendations show the these clinical practice guidelines have not succeeded in refining practice. Specifically, CK-MB is still used in many US clinical pathology laboratories and US EDs. 12,13 Based on the College of American Pa- thologists proficiency survey in 2013, 1558 of 1995 national US laboratories (77%) still use CK-MB. 12 In 2009, Parker and Suter 13 sur- veyed 98 ED physician leaders in 21 academic and 77 community EDs regarding the use of cardiac biomarkers and found that 77% (76 of 98) still use CK-MB. Collinson et al 14 found that of the nearly 40% of North American and European laboratories (n = 533) offer- ing CK-MB testing in 2006, 25% continued to offer the test even af- ter the national guidelines discussed above recommended against its use. Cappelletti et al 15 added to the findings by Collinson et al 14 by adding data from Italy (n = 126 laboratories) that showed 20.2% of laboratories continue to use CK-MB. This retention of CK-MB has been attributed to clinicians’ re- luctance to rely on cTn in certain clinical situations, as well as clini- cian familiarity. 8,11 In 2010, a study coauthored by 7 large academic medical centers labeled CK-MB as 1 of 10 tests that no longer pro- vide value, 16 and a growing number of medical centers have aban- doned use of CK-MB. 8 With the goal of advancing high value prac- tice, as defined by the ACC, ESC, AHA 3-5 and National Academy of Clinical Biochemistry, this implementation guideline is designed to 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

Creatine Kinase–Myocardial Band Testing in Suspected ACS Evidence-Based Guidelines: Troponin and CK-MB Tests
Creatine Kinase–Myocardial Band Testing in Suspected ACS Evidence-Based Guidelines: Troponin and CK-MB Tests

Evidence-Based Guidelines:

Troponin and CK-MB Tests

NumerousstudieshavecomparedCK-MBandcTnwith respect to their diagnostic precision related to the initial diagnosis of AMI, the assess- ment of reinfarction,and prognosisaftermajor cardiovascularevents. Cardiac troponin has been shown to be highly sensitive for AMI (99.2%) 17 and to be more specific than CK-MB (lower false-positive rate)owing toitsexclusivityincardiacmyocytes (vsCK-MB,whichmay be elevated with skeletal muscle damage). 16-19 Hawkins et al 20 cal- culateda specificity ofcTn testingas highas92%comparedwith40% for CK-MB. Lin et al 21 observed that among patients with suspected AMI who also had negative cTn results, approximately 10% of pa- tients had abnormally high CK-MB. 22 Similarly, Antman et al 23 evalu- ated cardiac biomarker levels in patients with ACS symptoms and found that 238 of 948 patients (25%) initially classified as having un- stable angina owing to normal CK-MB tests actually had elevated cTn levels. Thus, the use of CK-MB may potentially misclassify individu- als with ACS by mistakenly diagnosing unstable angina in some pa- tients with true myocardial infarction. In patients with chronic renal disease, the diagnosis of ACS can be challenging, as cTn levels may be chronically elevated. H owever, CK-MB has been shown to provide no incremental value over cTn in the diagnosis of ACS in patients with chronic renal disease. 24,25 In fact, CK-MB levels are often elevated in patients on dialysis in the absence of ACS signs and/or symptoms. 25 In terms of time to diagnosis, both CK-MB and troponin are equally rapid in ACS diagnosis, 8 but with more sensitive assays, cTn rises much more rapidly. 26-28 In addition to its superior sensitivity and specificity, cTn yields stronger prognostic information. In pa- tients with ACS, the CRUSADE investigators (n = 29 357) 29 showed that elevated cTn is associated with in-hospital mortality, regard- less of CK-MB levels. H owever, when CK-MB levels are elevated in the presence of a normal cTn, in-hospital mortality is comparable to CK-MB levelsand cTn both being negative. 29-31 Most important, those with elevated CK-MB values but normal cTn levels do not manifest an adverse prognosis. 29-31 Despite a longstanding, commonly held physician belief that CK-MB is more useful than cTn for detecting reinfarction, no study has shown that CK-MB levels are superior to cTn in this regard. 32,33 Indeed,most data confirm that cTn provides far better estimates be- cause it is less impacted by changes in the amount of marker re- leased with reperfusion. 34 Single values correlate closely with in- farct size as determined by cardiac magnetic resonance imaging. 35 Apple et al 36 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 Most patients with ACS are treated with either surgical or per- cutaneous revascularization. 37,38 The use of CK-MB or cTn follow- ing percutaneous coronary intervention (PCI) is controversial, as there is no current consensus regarding the definition, prognosis, and subsequent treatment of periprocedural myocardial infarction diagnosed by cardiac biomarker elevation alone. Some groups have suggested that CK-MB is superior to cTn in terms of detecting peri- procedural myocardial infarction, 38 while others have argued that post-PCI cardiac biomarkers are not useful because prognosis is re- lated to the pre-PCI cTn value, and when that is taken into account,

post-PCI myocardial injury is not an important clinical end point. 39 Even if clinicians decide to assess cardiac biomarkers in this setting, post-PCI cTn and CK-MB values provide equally accurate prognos- tic information. 39 Because this guideline is focused on cardiac bio- marker use in routine ACS diagnosis, rather than cardiac biomarker use following PCI, we defer further discussion and/or recommen- dation with respect to this ongoing clinical controversy. Another potential area of controversy concerns the appropri- ate use of cTn in clinical practice. 40 The major strength of using cTn—its specificity for cardiac injury—is also a potential shortcom- ing, because cTn detects myocardial injury irrespective of the spe- cific cause. Consequently, many noncardiac conditions associated with secondary myocardial injury, such as pulmonary embolus, se- vere anemia, and severe hypotension from any cause, are associ- ated with abnormal cTn. Wilson et al 40 reported a high prevalence of elevated cTn in a large group of hospitalized patients due to non- cardiac conditions and has suggested that this may represent an ex- ample of overuse of cTn. Another group has reported a small series of patients in which the quantity of troponins ordered per patient exceeded guideline recommendations. 41 We acknowledge that the real-world use of cTn, with respect to appropriate clinical indica- tion and quantity over time, deserves further study and quality im- provement initiatives designed to refine usage. Finally, Saenger et al 8 have observed that concomitant use of CK-MB and cTn is often confusing for physicians, and they are aware of situations in which such confusion has negatively affected pa- tient care. An example of a potentially confusing clinical situation is when a patient is admitted with possible symptoms of ACS and is found to have an abnormally elevated CK-MB levels in the setting of sequentially normal troponin levels. Although normal sequen- tial troponin values exclude the diagnosis of acute myocardial injury—and are associated with a favorable short-term prognosis regardless of the CK-MB levels—some physicians might errone- ously conclude that the patient has suffered acute myocardial injury due to CK-MB elevation. Others might wonder if there is another condition (ie, skeletal muscle breakdown) responsible for the CK-MB elevation and might erroneously devalue the impor- tance of the patient’s symptoms and electrocardiogram in making the diagnosis of ACS. 42 We would argue that elimination of rou- tine CK-MB ordering is not only high value because it offers no benefit and results in considerable cost but also because elimina- tion of CK-MB may reduce physician confusion, improve under- standing of the proper use of cTn, and consequently reduce potential patient harm.

use of cTn, and consequently reduce potential patient harm. Safety and Quality Outcomes Data: Eliminating CK-MB
use of cTn, and consequently reduce potential patient harm. Safety and Quality Outcomes Data: Eliminating CK-MB

Safety and Quality Outcomes Data:

Eliminating CK-MB Testing

Multiple academic medical centers have implemented interventions to eliminate the routine ordering of CK-MB and measured associ- ated cost savings and impact on patient safety ( Table ). 12,43-46 Larochelle et al 44 recorded data on patients with suspected ACS (n = 60 494 patients preintervention; n = 24 341 patients postinter- vention) over a period of 43 months (31 months preintervention; 12 months postintervention). They initially developed an institutional guideline in collaborationwith cardiologists to specify appropriate or- 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 system when physicians searched for CK-MB, tracked searches/Orders by provider Restricted CK-MB testing to patients who were post-PCI and postcardiac surgery

87% reduction in CK-MB tests (n = 1106 to 139/mo) Fewer orders after searches for CK-MB testing Fewer searches for CK-MB testing Physicians who had not seen the BPA (0 prior searches) were more likely ( P < .01) to place a search

Larochelle et al, 44 2014

84 835

12 mo

Developed institutional guideline in consultation with cardiologists to order 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

95% reduction in CK-MB tests with $720 000 in annual savings No decrease in ACS incidence

Singh and Baweja, 12 2014

37 418

6 y

Removed CK-MB testing from CPOE ACS routine order sets Reviewed cases (n = 171) where CK-MB tests were still ordered

99.8% reduction in CK-MB tests (12 057 in 2007, 36 in 2013) No CK-MB test for the 171 patients provided diagnostic or prognostic value

Le et al, 45 2015

14 571

12 mo

Removed CK-MB testing from CPOE ACS routine order sets

80% reduction in CK-MB tests 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 CPOE ACS routine order sets

84% reduction in CK-MB tests (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.

Figure 1. Best Practice Alert Example

Best Practice Alert – CK-MB Lab Test

Based on national evidence-based guidelines 1,2,3 :

- Troponin is the preferred marker in diagnosing AMI/ACS - CK-MB in addition to troponin adds no incremental diagnostic value

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 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 Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 64:e139-228.

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.

An example of a Best Practice Alert to appear in the physician ordering system when attempting to order a creatine kinase–myocardial band.

advised practitioners to order cTn alone, without CK-MB. The au- thors then implemented multiple interventions, including educa- tional sessions for internal medicine and ED physicians, dissemina- tion of pocket-sized quick reference cards with the recommended orderingalgorithm,and removalofCK-MB fromACS routineorder sets within the computerized provider order entry (CPOE) system. A Best Practice Advisory (BPA)was created in the CPOE system using the in- stitutional guideline to alert physicians who attempted to order CK- MB. Physicians could, if desired, order CK-MBmanually. By 12months postintervention, the estimated number of CK-MB tests per patient was0, representing an absolute change of −0.96 CK-MB tests per pa-

tient (95% CI, −1.00 to −0.92). The authors estimated a 95% reduc- tion in CK-MB tests, translating to $720 000 in annual savings. Similarly, Baron et al 43 removed CK-MB from routine order sets and implemented a BPA into their CPOE system without additional educational sessions. After only 2months postimplementation, they noted an 87% decrease in CK-MB orders. In addition, they noted fewer orders after searches and fewer searches for CK-MB over this time, arguing for a long-term educational benefit for the BPA. Mul- tiple other groups, including Mayo Clinic, simply removed CK-MB from routine order sets and found 80.0% to 99.8% reductions in CK-MB orders with significant cost savings and without negative im- pact on patient care or missed AMI diagnoses. 8,12,43-46

care or missed AMI diagnoses. 8 , 1 2 , 4 3 - 4 6 Implementation
care or missed AMI diagnoses. 8 , 1 2 , 4 3 - 4 6 Implementation

Implementation Blueprint:

Eliminating CK-MB Testing

With clear evidence to support elimination of CK-MB from clinical care for the diagnosis of ACS and based on experience eliminating CK-MB at our respective institutions,we devised a blueprint for other institutions to use in enacting quality improvement initiatives. The methodology and theory of the blueprint and quality improve- ment initiative are based on the US Health Resources and Services Administration strategies for developing and implementing a qual- ity improvement initiative, with a focus on education, action, and measurement of results. 47 The leader of each institution should

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Clinical Review & Education Special Communication

Figure 2. Pocket Card

High Value Practice Academic Alliance Pocket Card Cardiac Biomarker Ordering for ACS/AMI

Obtain troponin

Card Cardiac Biomarker Ordering for ACS/AMI Obtain troponin you suspect Acute Coronary Syndrome (ACS) /Acute Myocardial

you suspect Acute Coronary Syndrome (ACS)/Acute Myocardial Infarction (AMI)

Coronary Syndrome (ACS) /Acute Myocardial Infarction (AMI) Initial presentation   6-9 hours later 12-24

Initial presentation

 

6-9 hours later

6-9 hours later

12-24 hours later symptoms

intermediate to high clinical suspicion and/or recurrence of

STOP CHECKING. If troponin is abnormal:

• correlate with clinical presentation to determine likihood of ACS

• there is no utility to trending abnormal troponin to peak or resolution

•

patient has ACS,

there is clinical concern for reinfarction, additional

troponin measurements may be useful

CK-MB in addition to troponin offers no incremental diagnostic value.

addition to troponin offers no incremental diagnostic value. An example of a pocket card for mass

An example of a pocket card for mass distribution to faculty and house staff regarding creatine kinase–myocardial band and troponin testing.

assess applicability of this blueprint based on the CK-MB ordering frequency at their respective institution.

1. Design and implement a hospital-wide educational campaign.

Prior to implementation, it is important for health care leaders to establish sufficient organizational readiness for change, spe- cifically in conjunction with these stakeholders, whose order- ing practices will be affected by such changes. Tools to mea- sure readiness for change have been previously studied andmay be used. 48,49

Collaboratewithphysician representatives from thedepartments ofcardiology,internalmedicine,andemergencymedicine. Front- line physicians in these departments order the majority of car- diac biomarkers withinmost health care institutions and are the primary stakeholders in the current system of care for ACS patients.

Academic institutions must engage the house staff as members 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 changes.

Inform physicians that CK-MB adds to the health care system financial burden without adding value to patient care.

Present the evidence supporting elimination of CK-MB and ex- clusive use of cTn to diagnose AMI, identify reinfarction, and es- timate infarct size. Education may be provided through vari- ous venues, including lectures, pocket cards ( Figure 2 ), online modules, social media demonstrations, and simulations. 44

Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS

2. Partner with information technology and/or laboratory medi- cine staff to remove CK-MB from standardized ACS routine order sets. Doing this simple step alone has been shown to sig- nificantly reduce CK-MB ordering (Table). 8,12,45,46

3. Partner with information technology and/or laboratory medi-

cine staff to create and integrate a best practice alert into the CPOE to appear when clinicians order CK-MB, such as:

According to national guidelines, troponin is the preferred bio- marker for detecting myocardial injury; CK-MB is only appro- priate if troponin testing is unavailable. Figure 1 provides an example. 43,44

4. Measure data preintervention and postintervention (efficacy

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, andmortality of AMI to ensure pa- tient safety.

Review cases where CK-MB is still ordered to determine if it provides value.

If necessary, track usage by physician to develop performance feedback profiles.

Calculate reduction in charges to patients and health plans, as well as any decrease in hospital costs. Though seemingly straightforward to articulate, we acknowl- edge that significant barriers to implementationexist,and in this case the biggest hurdle has been convincing physicians who have or- dered CK-MB for years to change their practice. Successful deimple- mentation of CK-MB requires leadership support, education, and re- assurance that diagnostic efficacy will not be compromised. Other challenges relate tomanpower as well asmodifications and data col- lection from the electronic medical record. To optimize manpower, academic centers can engage house staff because this will also ensure longstanding change. Again, leadership commitment to al- locating information technology resources for data collection and clinical decision support tools is critical.

collection and clinical decision support tools is critical. Conclusions Creatine kinase–myocardial band testing
collection and clinical decision support tools is critical. Conclusions Creatine kinase–myocardial band testing

Conclusions

Creatine kinase–myocardial band testing provides no incremental value to patient care, and its elimination can lead tomillions of health care dollars saved without adversely affecting patient care. This is backed by both strong evidence-based guidelines and experiences from multiple institutions. The blueprint presented here should be carefully considered by health care leaders and clinicians as the first step to finally putting the CK-MB laboratory test to rest.

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ARTICLE INFORMATION

Accepted for Publication: June 12, 2017.

Published Online: August 14, 2017. doi: 10.1001/jamainternmed.2017.3597

Author Affiliations: Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, Maryland (Alvin); Division of Cardiology, Department of Medicine, Mayo Clinic, Rochester, Minnesota (Jaffe); Division of Cardiology,

Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland (Ziegelstein, Trost).

Conflict of Interest Disclosures: None reported.

Acknowledgements: This article is the first collaborative scholarly activity produced by faculty in the High Value Practice Academic Alliance (HVPAA). The HVPAA organization includes faculty from more than 80 academic medical centers

collaborating on quality improvement, research, and education related to high-value healthcare.

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Eliminating Creatine Kinase–Myocardial Band Testing in Suspected ACS

Special Communication Clinical Review & Education

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