Solomon et al. AppendixPage 1

Appendix

Statistical method for testing differences in physician decisions.

A permutation approach was used to test for differences in the percentages of physician treatment decisions before and after seeing the CHDRA test results. A binary index was created for each treatment decision (0: not adhering to guidelines, 1:adhering to guidelines before and after seeing the CHDRA result). The indices were then randomly permuted, as a block for each physician, between the before and after categories and the percent agreement with guidelines was calculated. The percent values were transformed using a logit function and the differences between the before and after values were calculated. The random permutation process was repeated 1000 times to generate a null distribution for the differences. The difference of the logits of the observed percentages was compared to the null distribution leading to the estimation of a two sided p-value.

CHDRA Clinical Utility Survey Summary

The following vignettes present a clinical outpatient encounter that incorporates CHDRA results. Each case is an actual patient from the clinical study. You will be asked a series of questions to indicate how you would use those results in managing the patients’ coronary heart disease risk factors if they were one of your patients.

CASE #1

History of Present Illness / A 62 year-old male with self reported family history of high blood pressure presents for his annual physical.
Past Medical History / Hypertension
Medications / calcium channel blocker, diuretic, and daily aspirin
Social History / Non Smoker
Family History / No family history of coronary artery disease
Physical Exam / Value / Reference Range
Height / 5’9”
Weight (lbs.) / 173
BMI / 25.6 / 18.5-24.9
Blood Pressure / 136/80 / Normal <120/<80
Prehypertension 120-139/ 80-89
Laboratory Results
Total Cholesterol (mg/dL) / 123 / <200 (mg/dL)
LDL (mg/dL) / 77 / <100 optimal; 100-129 Near optimal; 130-159 Borderline high; 160-189 High; >=190 Very high
HDL (mg/dL) / 34 / 40 = Low
> 60 = High
Triglycerides (mg/dL) / 73 / <150 (mg/dL)
CRP (mg/L) / 8.3 / 0.1 -0.82 (mg/dL)
Fasting Glucose (mg/dL) / 89 / <110
Creatinine (mg/dL) / 0.8 / Female: 0.55-1.02
Male: 0.73-1.18

Upon reviewing these results, how would you stratify this patient’s coronary heart disease risk?

  • Low risk
  • Intermediate risk
  • High risk
  • Unable to determine from the information provided

How would you treat/manage this patient (assuming no contraindications to any medications)?

Medical history and physical exam
Measurement of fasting lipids
Measurement of fasting glucose /
  • Every one month
  • Every three months
  • Every six months
  • Once per year
  • Every two years
  • Every five years
  • I wouldn’t monitor this

What lifestyle changes do you suggest to manage this patient? (Please select all that apply)

Continued abstinence from tobacco use

DASH-like diet (Dietary Approaches to Stop Hypertension)

Increase intake of fruit and vegetables

Regular physical activity

Weight management

None of these

Which specialists would you refer to manage this patient? (Please select all that apply)

Cardiologist

Preventive cardiologist

Nutritionist / Dietician

Other (Please specify):______

I would not refer this patient to a specialist (exclusive)

Which of the following medical therapies would you initiate for this patient based on the following clinical and laboratory values:

aspirin/antiplatelet for primary prevention (assuming no contraindications)

  • ASA 81mg daily
  • ASA 325mg daily
  • Clopidogrel 75mg daily
  • No therapy change indicated
  • I wouldn’t initiate anything for this
  • Remove from Aspirin therapy

Which of the following medical therapies would you initiate for this patient based on their LDL level:

  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 160
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 130
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 100
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 70
  • Lipid therapy to achieve non-HDL cholesterol < 130
  • Lipid therapy (i.e., statin, niacin) regardless of LDL level
  • No therapy indicated

Based on the patient’s current therapy, would you change or add a hypertensive agent?

Hydrochlorothiazide

Beta-blocker

ACE-Inhibitor

Angiotensin receptor blocker

Calcium channel blocker

Long-acting nitrates

Hydralazine

Alpha-blocker

Other anti-hypertensive medication

  • No therapy indicated

What noninvasive imagingand/or invasive testing would you order for this patient? (Please select all that apply.)

ECG

Exercise Treadmill Test

Resting echocardiogram

Stress echocardiogram

Stress nuclear perfusion study

Coronary calcium score

Coronary computed tomography (CT) angiogram

Magnetic resonance (MRI) coronary

Coronary angiogram

None of these (exclusive)

This patient was found to be intermediate risk for a coronary event. A CHDRA test was performed.

The CHDRA 5-year risk was 13.0%, equating to a 4.3 times increased risk compared to the average age- and sex-matched risk, which is 3.0%.

This places the patient at high risk for an MI or unstable angina in the next 5-years.

The CHDRA risk category scale is as follows:

Low Risk: 0-3.49%

Intermediate Risk: 3.50 – 7.49%

High Risk: >7.5%

Does knowing the CHDRA score change your management/treatment of the patient?

Your previous answers are below. Please select those that you would change based on knowing the CHDRA score for this patient.

Medical history and physical exam – frequency value inserted in from Q.16
Measurement of fasting lipids – frequency value inserted in from Q. 16
Measurement of fasting glucose – frequency value inserted in from Q. 16 /
  • This wouldn’t change
  • Every one month
  • Every three months
  • Every six months
  • Once per year
  • Every two years
  • Every five years
  • I wouldn’t monitor this

Given the CHDRA score, what lifestyle changes do you suggest to manage this patient? (Please select all that apply)

Continued abstinence from tobacco use

DASH-like diet (Dietary Approaches to Stop Hypertension)

Increase intake of fruit and vegetables

Regular physical activity

Weight management

  • None of these

Given the CHDRA score, which specialists would you refer to manage this patient? (Please select all that apply)

Cardiologist

Preventive cardiologist

Nutritionist / Dietician

Other (Please specify):______

I would not refer this patient to a specialist (exclusive)

Does knowing the CHDRA score change the medical therapies you would initiate?

Your previous answers are below. Please select those that you would change based on knowing the CHDRA score for this patient.

Aspirin/antiplatelet for primary prevention (assuming no contraindications)

  • This wouldn’t change
  • ASA 81mg daily
  • ASA 325mg daily
  • Clopidogrel 75mg daily
  • No therapy change indicated
  • I wouldn’t initiate anything for this
  • Remove from Aspirin therapy

Does knowing the CHDRA score change the medical therapies you would initiate?

Your previous answers are below. Please select those that you would change based on knowing the CHDRA score for this patient.

Lipid lowering therapy based on this patient’s LDL level

  • This wouldn’t change
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 160
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 130
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 100
  • Lipid therapy (i.e., statin, niacin) to achieve LDL < 70
  • Lipid therapy to achieve non-HDL cholesterol < 130
  • Lipid therapy (i.e., statin, niacin) regardless of LDL level
  • No therapy indicated

Does knowing the CHDRA score change the medical therapies you would initiate?

Your previous answers are below. Please select those that you would change based on knowing the CHDRA score for this patient.

Anti-hypertensive therapy based on this patient’s current therapy

  • This wouldn’t change

Hydrochlorothiazide

Beta-blocker

ACE-Inhibitor

Angiotensin receptor blocker

Calcium channel blocker

Long-acting nitrates

Hydralazine

Alpha-blocker

Other anti-hypertensive medication

  • No therapy indicated

Given the CHDRA score, what noninvasive imagingand/or invasive testing would you order for this patient? (Please select all that apply.)

ECG

Exercise Treadmill Test

Resting echocardiogram

Stress echocardiogram

Stress nuclear perfusion study

Coronary calcium score

Coronary computed tomography (CT) angiogram

Magnetic resonance (MRI) coronary

Coronary angiogram

  • None of these (exclusive)

The CHDRA score provides further information on this patient’s coronary risk and reclassified the patient from intermediate risk to high risk. The CHDRA score was 13.0%. This patient did experience a cardiac event within the 5-years.

To what degree do you agree this information is useful to appropriately manage the patient?

  • Strongly agree
  • Somewhat agree
  • Neither agree nor disagree
  • Somewhat disagree
  • Strongly disagree

(Above case presentation and series of questions asked for 2 more cases)

After Case Study #3:

Following your use of the CHDRA Assessment in making patient care decisions in the previous case studies, to what degree do you see value in incorporating the CHDRA score in your practice to further stratify intermediate risk patients?

I find the CHDRA Assessment to be:

  • Extremely valuable
  • Valuable
  • Slightly valuable
  • Not at all valuable

Please indicate your level of agreement with each of the following statements. The CHDRA Assessment and its results…

Is compelling and caught my attention.
Is likely to have a significant impact on my patient management choices and treatment decisions.
Is likely to have a significant impact on patient behavior by presenting the information to patients.
Has provided me with valuable information that I did not know before. /
  • Strongly agree
  • Somewhat agree
  • Neither agree nor disagree
  • Somewhat disagree
  • Strongly disagree

Please rate your willingness to recommend the CHDRA Assessment to your colleagues based on the scale below:

  • 0 – Extremely unlikely to recommend
  • 1
  • 2
  • 3
  • 4
  • 5 – Extremely likely to recommend

Given the information about CHDRA presented to you, which of the following best represents your thoughts?

  • CHDRA is very interesting and would like to try it in my practice as soon as I can
  • CHDRA is somewhat interesting and would consider trying it with a little more information
  • CHDRA is marginally interesting but I would need significantly more information to try it in my practice
  • CHDRA is not interesting to me

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Solomon et al. AppendixPage 1

Appendix Table 1.Change in frequency of physical examinations in cases 1,2,3,4,7 which were reclassified from intermediate to high risk.

Frequency of Physical Exams, After Seeing CHDRA Results
1/ Mo / 1/3 Mo / 1/6 Mo / 1/ Yr / 1/2 Yr / 1/5 Yr / Never
Frequency of Physical Exams, Initial
1/ Mo / 10 / 0 / 0 / 0 / 0 / 0 / 0
1/3 Mo / 5 / 89 / 2 / 0 / 1 / 0 / 0
1/6 Mo / 3 / 39 / 87 / 4 / 0 / 0 / 1
1/ Yr / 1 / 7 / 45 / 100 / 0 / 0 / 0
1/2 Yr / 0 / 1 / 0 / 1 / 1 / 0 / 0
1/5 Yr / 0 / 0 / 1 / 0 / 0 / 0 / 0
Never / 0 / 0 / 0 / 0 / 1 / 1 / 0

p value <0.0001 from Bhapkar test calculated after substituting 0.00001 for 0 in above table (null hypothesis of the same frequency of physical examinations before and after seeing CHDRA results.)

Appendix Table 2. Views on incorporating CHDRA to further stratify intermediate risk individuals.

Physician Specialty
Cardiology, %
(n=50) / Internal Medicine, %
(n=51) / Family Practice, %
(n=54) / OB/GYN), %
(n=51) / All, %
(n=206)
Extremely Valuable / 14 / 22 / 17 / 24 / 19
Valuable / 48 / 49 / 61 / 51 / 52
Slightly Valuable / 30 / 27 / 20 / 25 / 26
Not At All Valuable / 8 / 2 / 2 / 0 / 3

No statistically significant differences between the physician specialties were observed at p<0.05 using a z test of proportions.

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Appendix Table 3.Physician’s likelihood of recommending CHDRA to colleagues.

Physician Specialty
Cardiology, %
(A, n=50) / Internal Medicine, %
(B, n=51) / Family Practice, %
(C, n=54) / OB/GYN), %
(D, n=51) / All, %
(n=206)
0 (unlikely) / 4.0 / 1.9 / 1.8 / 3.9 / 2.9
1 / 6.0 / 9.8 / 3.7 / 5.9 / 6.3
2 / 10.0 / 11.7 / 11.1 / 5.9 / 9.7
3 / 34.0 / 21.6 / 25.9 / 23.5 / 26.2
4 / 28.0C / 31.4 / 50.0 / 47.0 / 39.3
5 (extremely likely) / 18.0 / 23.5C / 7.4B / 13.7 / 15.5

Superscript letters indicate statistically significant differences between the physician specialties at p<0.05 using a z test of proportions.

Appendix Table 4. Physician’s agreement with statements about CHDRA*

Physician Specialty
Cardiology
%
(A, n=50) / Internal Medicine
%
(B, n=51) / Family Practice
%
(C, n=54) / OB/GYN
%
(D, n=51) / All
%
(n=206)
The CHDRA Assessment and its results are compelling and caught my attention. / 72D / 78.5 / 88.8 / 88.3 / 82.0
The CHDRA Assessment and its results is likely tohave a significant impact on my patient management choices and treatment decisions. / 62 / 72.5 / 74.1 / 76.5 / 71.3
The CHDRA Assessment and its results is likely to have a significant impact on patient behavior by presenting the information to patients. / 70 / 66.7 / 74.1 / 82.3 / 73.3
The CHDRA Assessment and its results has provided me with valuable information that I did not know before. / 62C,D / 76.4D / 87 / 94.1 / 80.1

*Physicians who stated they agree or strongly agree on a 5-level Likert scale.

Superscript letters indicate statistically significant differences between the physician specialties at p<0.05 using a z test of proportions.

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