Screening For Asymptomatic Obstructive Coronary Artery Disease Among High-Risk Diabetic Patients Using CT Angiography, Following Core 64

Screening For Asymptomatic Obstructive Coronary Artery Disease Among High-Risk Diabetic Patients Using CT Angiography, Following Core 64: A Randomized Control Study (The faCTor-64 Study)

Patients with a known history of diabetes mellitus and no prior documented evidence of cardiovascular disease will be evaluated for inclusion in the study. Once qualified, patients will be enrolled and be randomized to either the Control Arm or to the Asymptomatic Screening Arm. Patients in the Control Arm will be followed by their primary care physicians with the recommendation that they follow standard guidelines for management of diabetic patients.

Patients in the Asymptomatic Screening Arm will undergo CT screening for either coronary calcium scoring or multi-slice CT angiography as well as be placed on one of two medical regimens. Patients will be followed by telephone at six-month intervals for a minimum of one year for both primary and secondary outcomes.

Management of Patients Randomized to the Control Arm: Subjects randomized to the control arm will continue to be followed by their primary care physicians with the recommendation that they follow standard guidelines for management of diabetic patients.

Management of Patients Randomized to the Asymptomatic Screening Arm: Subjects randomized to the Asymptomatic Screening arm will undergo initial CT screening in the following fashion:

• Subjects with serum creatinine of < 2.0 mg/dl (men) or <1.8 mg/dL (women) will be screened using multi-slice CT angiography with contrast.
• Those with serum creatinine ≥ 2.0 mg/dl (men) or >1.8 mg/dL (women) will be screened without contrast to obtain a coronary calcium score. Further cardiac screening will be determined based on these results.

Subjects Receiving Multi-Slice CT Angiography (serum creatinine of < 2.0 mg/dl (men) or <1.8 mg/dL (women)): Subjects severe stenosis will proceed to coronary angiography and revascularization as needed. Subjects with moderate stenosis will be referred for adenosine stress cardiac MRI. If ischemia is detected, they will also be referred for coronary angiography. Subjects with either mild stenosis or normal coronary arteries will receive no further imaging studies.

Subjects Undergoing CT Evaluation for Coronary Calcium Scoring (serum creatinine ≥ 2.0 mg/dl (men) or >1.8 mg/dL (women): Subjects with coronary calcium scores >100 or >75th percentile will be referred for adenosine stress cardiac MRI. If ischemia is detected, they will be referred for coronary angiography. Subjects with coronary calcium scores = 0-10 or 11-100 and <75th percentile will receive no further imaging studies.

Medical Management (Only for those patients randomized to the Asymptomatic Screening Arm): In addition to the imaging studies and potential coronary revascularization procedures performed as described above, all subjects will be placed on one of two medical regimens:

• Standard Appropriate DM Care and
• Aggressive Risk Factor Reduction Care.

Standard Appropriate DM Care: Subjects assigned to this form of medical care will be managed by their primary physicians. This type of care will consist of targeting the goals proposed by Intermountain Healthcare for all patients with diabetes. These include the following three targets: HgA1C <7.0%, LDL cholesterol <100 mg/dL and Systolic BP<130 mm Hg. Subjects assigned to Standard Care will include all control subjects, as well as all screened subjects with either a normal CT angiogram or a coronary calcium score = 0-10.

Aggressive Risk Factor Reduction Care: Subjects assigned to this form of medical care, in addition to standard medical care provided by their primary physicians, will also be managed by their primary physicians, but will receive more aggressive risk factor reduction management according to a set of guidelines that will be given to the primary physicians. This aggressive management strategy, designed to address the increased medical risk among the asymptomatic diabetics with detected vascular disease, will consist of more aggressive glucose and lipid targets than is in the Standard Care protocols and specific medication algorithms designed to accomplish these more aggressive targets.

Follow-Up After enrollment into the protocol, all subjects will be followed for a minimum of one year. Follow-up will occur by telephone at six-month intervals. Outcomes will be ascertained by directly questioning the patient and by review of medical records. All primary outcomes will be adjudicated by an independent events committee.

Statistical Analysis Both an intention-to-treat analysis and a by protocol analysis will be performed. The intention-to-treat analysis will be the primary analysis and will be defined as all those randomized to scan versus all those randomized to control regardless of what actually happened. The by protocol analysis will be defined as all of those who actually got the protocol scan versus those who did not get the scan. Those who did not get the scan includes all those randomized to the control arm. If they went outside of the study and got a scan anyway, this will be considered to be for clinical indications and will still be in the non-protocol scan group. For those who were randomized to get the scan but never did, evaluation of their baseline characteristics will be made and if they did not differ from those who actually got the scan or from those who were randomized to control, then they will be included the didn't get scanned group.

Inclusion Criteria:

1. Age: Males ≥ 50 years; Females ≥55 years with: History of diabetes mellitus (prior documentation of fasting glucose ≥ 126 mg/dl or hemoglobin A1C > 6.5%), either type 1 or type 2, documented for at least 3 years and on medication for at least one year.
2. Age: Males ≥ 40 years; Females ≥45 years with: History of diabetes mellitus (prior documentation of fasting glucose ≥ 126 mg/dl or hemoglobin A1C > 6.5%), either type 1 or type 2, documented for at least 5 years and on medication for at least one year.
3. The patient or legally authorized representative must sign a written informed consent, prior to the procedure, using a form that is approved by the local Institutional Review Board.

Exclusion Criteria:

1. Known coronary artery disease (stenosis >70%, history of myocardial infarction, or angina)

2. Symptomatic cerebral vascular disease (history of TIA, CVA, or cerebrovascular [carotid or cerebral arteries] revascularization)

3. Symptomatic peripheral vascular disease (history of claudication, amputation, or peripheral [including renal arteries] arterial revascularization)

4. Treatment with any other investigational drug within the previous 30 days

5. Any therapy or condition that would pose a risk to the patient or make it difficult to comply with study requirements.

6. Pregnant and/or lactating women, and women of child bearing potential not using acceptable means of contraception. Women of childbearing potential must be using adequate measures of contraception (as determined by the Investigator) to avoid pregnancy and should be highly unlikely to conceive during the study period. Women of childbearing potential must have a negative pregnancy test at screen.

7. Any life threatening condition/significant co-morbidity such that primary screening is inappropriate.

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