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for some gastrointestinal bleeding. Since dabigatran
etexilate is a substrate for the p-glycoprotein enzyme,
potent inducers of the p-glycoprotein system, such as
rifampin, may result in localized increased levels of
dabigatran and more gastrointestinal bleeding. Several
common cardiac medications also make use of the
p-glycoprotein enzymes system including amiodarone and
verapamil. Increased levels of dabigatran are noted when
these drugs are combined, although the manufacturer
does not recommend a dose adjustment of dabigatran
when used with these drugs. There is concern about
the use of antiplatelet agents when used concomitantly
with dabigatran. Preliminary RE-LY data published in
abstract form at the European Society of Cardiology
2011 showed that when antiplatelet agents were used
in conjunction with warfarin, the risk of major bleeding
was 4.8%/year compared with 2.8%/year when warfarin
was not combined with antiplatelet agents. The risk of
major bleeding with dabigatran 150 mg twice daily was
4.4% when used in conjunction with antiplatelet agents
and 2.6%/year when dabigatran was not combined with
antiplatelet agent. Consequently, the clinician must
evaluate the need for aspirin and other antiplatelet agents
when using dabigatran.
Did RE-LY include patients different from clinical
practice? Currently, a registry is enrolling patients,
tracking the rate of major bleeding, myocardial infarction,
and other clinical events (ClinicalTrials.gov Identifier
NCT 01491178) which will help answer this important
question.
Dabigatran is a major advance in anticoagulant therapy
but should be used for the appropriate patient, at the
appropriate dose. I encourage physicians to follow the
guidelines listed by the manufacturer. The rapidity and
ferocity with which the US tort bar is creating a another
area of lucrative litigation against a new, useful drug that
is likely safer than drugs it will replace is, unfortunately, a
typical modus operandi.
Greg Flaker, MD
Professor of Medicine, Wes and Simone Sorenson Chair in
Cardiovascular Research, University of Missouri
MSMA Member since 2011
References
1. Food and Drug Administration. Drug Safety Communication – Safety review of
post-market reports of serious bleeding events. December 7, 2011.
2. Connolly S, Ezekowitz M, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J,
Reilly P, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis
B, Darius H, Diener H, Joyner C, Wallentin L, and the RE-LY Steering Committee
and Investigators. Dabigatran versus Warfarin in Patients with Atrial Fibrillation.
NEJM 2009;361:113-51.
3. Beasley B, Unger E, Temple R. Anticoagulant Options-Why the FDA Approved
a Higher but Not a Lower Dose of Dabigatran. NEJM 2011;364(19):1788-90.
ZŽůĞŽĨdĂůĐŝƵŵ^ĐŽƌŝŶŐŝŶ^ĐƌĞĞŶŝŶŐ
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In their excellent review “Update in the Management
of Coronary Artery Disease1,” in Missouri Medicine, March/
April 2012, 137-141, Drs. Stolker and Lim discussed
non-invasive imaging for assessment of patients with
known or suspected coronary artery disease (CAD). They
pointed out that the rapid evolution in the technology of
multi-slice computed tomography (CT) has allowed for
the development of high fidelity CT coronary angiography.
Although coronary CT angiography (CTA) is an efficient
and cost-effective strategy for promptly assessing patients
complaining of chest pain, this technique does involve
substantial radiation (5-11 mSv)2, exposure to a contrast
agent, and appreciable costs. As such, it is deemed
inappropriate by current CT Appropriate Use Criteria3 for
assessing people with low or intermediate probability of
CAD who are asymptomatic.
Non-contrast multi-slice CT is a useful screening
tool to identify and quantify coronary artery calcification
(CAC)4. This rapid and simple test provides powerful,
independent adjunctive information to identify individuals
with subclinical coronary atherosclerosis needing aggressive
cardiovascular (CV) risk factor modification.
The ACC and AHA recommend CAC scoring for
selected asymptomatic individuals at intermediate CAD
risk3. Recent SHAPE5 guidelines are more inclusive and
endorse CAC screening by a multi-slice non-contrast CT
to risk stratify middle-aged adults with more than one CV
risk factor. This translates to the majority of the adult
American population over age 45 years for males and 50
years for females. A CAC score has been found to be a
powerful, independent predictor of future CV morbidity
and mortality6-9 (See Figure 1). The coronary calcium
score has been shown to be more powerful than the
Framingham risk score (FRS) for predicting adverse CV
events in asymptomatic persons age 50 to 706. Between
various novel and emerging coronary heart disease (CHD)
risk markers, the CT CAC scoring was found to provide
the most incremental predictive power over and above that
provided by FRS assessment10. An abnormal CAC score has
also been shown to modify physician recommendations,
increase patient compliance with CV risk factor
modification suggestions and future follow-up with their
healthcare providers, and to lead to improved CV risk factor
profile11,12. A “0” calcium score (See Figure 2) is associated
with a very good cardiovascular prognosis for at least five
years. Additionally, CT CAC scoring is fast (the entire
acquisition can be obtained in a 15-20 second breath hold),
Missouri Medicine | May/June | 109:3 | 193
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coronary heart disease events in a large cohort of asymptomatic men and women. Am
J Epidemiol. 2005;162:421-429.
8. Raggi P, Shaw LJ, Berman DS, Callister TQ. Gender-based differences in
the prognostic value of coronary calcification. J Womens Health (Larchmt).
2004;13:273-283.
9. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary
 
events in four racial or ethnic groups. N Engl J Med. 2008;358:1336-1345.
‹‰—”‡ʹǣ
 10. Kavousi M, Elias-Smale S, Rutten JH, et al. Evaluation of newer risk markers
for coronary heart disease risk classification: a cohort study. Ann Intern Med.
2012;156:438-444.
11. Bybee KA, Lee J, Markiewicz R, et al. Diagnostic and clinical benefit of combined
coronary calcium and perfusion assessment in patients undergoing PET/CT
myocardial perfusion stress imaging. J Nucl Cardiol. 2010;17:188-196.
12. Rozanski A, Gransar H, Shaw LJ, et al. Impact of coronary artery calcium
scanning on coronary risk factors and downstream testing the EISNER (Early
Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research)
prospective randomized trial. J Am Coll Cardiol. 2011;57:1622-1632.

Editor’s Note
 Joshua M. Stoker, MD and Michael J. Lim, MD,
authors of the Missouri Medicine paper referenced in the
with a low radiation exposure (typically about 1 mSv)2 and above Letter to the Editor, declined to respond as the above
does not require IV access, contrast agent use, or stress. It is letter is self-explanatory. MM
now quite an inexpensive test at most institutions (the total
bill for a CT CAC scoring study at our institution is $49).
Harshal Patil, MD, James O’Keefe, MD, Check out the PPIA difference.
Randall Thompson, MD & Timothy Bateman, MD
Saint Luke’s Health System’s Taste Our Recipe for Success.
Mid America Heart & Vascular Institute
Kansas City
References
1. Stolker JM, Lim MJ. Update in the Management of Coronary Artery Disease.
Missouri Medicine March/April;109:2:137.
2. Koshy S, Thompson RC. Review of radiation reduction strategies in clinical
cardiovascular imaging. Cardiol Rev. 2012;20:139-144.
3. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/
NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography.
A report of the American College of Cardiology Foundation Appropriate Use Criteria
Task Force, the Society of Cardiovascular Computed Tomography, the American
College of Radiology, the American Heart Association, the American Society of
Echocardiography, the American Society of Nuclear Cardiology, the North American
Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and
Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll
Cardiol. 2010;56:1864-1894.
4. Budoff MJ, Cohen MC, Garcia MJ, et al. ACCF/AHA clinical competence statement
on cardiac imaging with computed tomography and magnetic resonance: a report
of the American College of Cardiology Foundation/American Heart Association/
American College of Physicians Task Force on Clinical Competence and Training. J Am
Coll Cardiol. 2005;46:383-402.
5. Naghavi M, Falk E, Hecht HS, et al. From vulnerable plaque to vulnerable patient-
-Part III: Executive summary of the Screening for Heart Attack Prevention and
Education (SHAPE) Task Force report. Am J Cardiol. 2006;98:2H-15H.
Professional Physicians Professional
Indemnity Association
6. Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calcification,
liability insurance 3218 Emerald Lane, Suite B
coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular Jefferson City, MO 65109
for Missouri physicians 
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disease events: the St. Francis Heart Study. J Am Coll Cardiol. 2005;46:158-165.
7. LaMonte MJ, FitzGerald SJ, Church TS, et al. Coronary artery calcium score and

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