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

Nov 17, 2014
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Intermountain Research and Medical Foundation, Intermountain Healthcare Urban Central Region, Intermountain Heart Institute Department of Cardiovascular Research, Toshiba Corporation, and Bracco Corporation
Date Presented:
01/01/2014
Date Published:
01/01/2014
Date Updated:
11/17/2014
Original Posted Date:
11/17/2014
References

Description:

Patients with diabetes have a high risk of adverse cardiac events. The current trial sought to study the efficacy of routine screening for coronary artery disease (CAD) in patients with type 1 or 2 diabetes and no overt symptoms of CAD.

Hypothesis:

CAD screening with coronary computed tomography angiography (CCTA) in patients with diabetes mellitus (DM) and no known CAD would reduce cardiovascular (CV) outcomes compared with routine management.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Men: ≥50 years old with at least a 3-years history of DM or ≥40 years old with at least a 5 year history of DM
  • Women: ≥55 years old with at least a 3-year history of DM or ≥45 years old with at least a 5-year history of DM
  • Use of antidiabetic medication for at least 1 year

    Number of screened applicants: 14,208
    Number of enrollees: 900
    Duration of follow-up: 4 years
    Mean patient age: 61.6 years
    Percentage female: 48%

Exclusions:

  • Documented atherosclerotic CV disease (known CAD, history of MI, angina, erebrovascular accident, transient ischemic attack, cerebral or peripheral revascularization)
  • Limited life expectancy or comorbidity

Primary Endpoints:

  • Composite of all-cause mortality, nonfatal MI, and hospitalization for unstable angina

Secondary Endpoints:

  • CV death alone and together with MI and unstable angina
  • CAD death alone and together with MI and unstable angina
  • Hospitalization for heart failure
  • Rise in serum creatinine by ≥0.5 mg/dl at 30 days and persisting at 1 year
  • Stroke or carotid revascularization procedure

Drug/Procedures Used:

Routine CCTA-guided CAD screening and directed therapy would be superior to routine management in CV risk reduction in patients with DM of at least 3-5 years’ duration. Coronary arteriography and coronary artery calcium (CAC) levels were performed on a Toshiba Aquillon 64 CT scanner. Only a CAC score was obtained if creatinine ≥2.0 mg/dl (men) or ≥1.8 mg/dl (women), contrast allergy, or heart rate >60 bpm. Scan results were classified as severe stenosis (≥70% stenosis in at least one major proximal or large coronary artery; recommendation to pursue coronary angiography), moderate stenosis (50-69% stenosis or CAC >100; recommendation to pursue stress testing), mild stenosis (10-49% stenosis or CAC >10-100; no further imaging recommended) or normal (<10% stenosis and CAC ≤10; no further imaging recommended).

Concomitant Medications:

Diabetes appropriate care was recommended. Statin use was 74%.

Principal Findings:

A total of 900 patients were randomized, 452 to CCTA and 448 to routine management. Baseline characteristics were fairly similar between the two arms. Mean duration of DM was 13 years, and 20% were on insulin only, with another 23% on both insulin and noninsulin agents. The mean glycated hemoglobin (HbA1c) was 7.5%, with a mean low-density lipoprotein cholesterol of 87 mg/dl. In the CCTA arm, the median CAC score was 55, with 41% having Agatston scores ≥100. About 21% had moderate or severe stenosis on CCTA. An aggressive medical regimen was adopted in 70% of subjects in the CCTA arm. About 14% had protocol-dependent percutaneous coronary intervention in the CCTA arm.

The primary endpoint was similar between the CCTA and routine management arms (6.2% vs. 7.6%, hazard ratio 0.8, 95% confidence interval 0.49-1.32, p = 0.38). All-cause mortality (3.5% vs. 4.3%, p = 0.56), nonfatal MI (1.5% vs. 1.8%, p = 0.72), CV death (1.5% vs. 1.8%, p = 0.76), CAD death (1.1% vs. 0.4%, p = 0.29) and stroke/carotid revascularization procedure (1.8% vs. 2.0%, p = 0.73) were all similar between the two arms; hospitalization for congestive heart failure was lower in the CCTA arm (0.7% vs. 2.2%, p = 0.04).

Interpretation:

The results of this trial indicate that routine screening for CAD in asymptomatic patients with DM using CCTA was not beneficial in reducing CV events compared with routine management. Despite finding moderate to severe CAD in 1 out of every 5, and a high Agatston score in 4 out of 10 asymptomatic patients with DM, the event rates in both arms were low, approximately 0.5% annual rate of myocardial infarction (MI). This reinforces the importance of aggressive risk factor and lifestyle modification in these patients. In the earlier DIAD trial, CAD screening using stress imaging in a similar population had not shown a beneficial effect for CV outcomes.

References:

Muhlestein JB, Lappé DL, Lima JA, et al. Effect of Screening for Coronary Artery Disease Using CT Angiography on Mortality and Cardiac Events in High-Risk Patients With Diabetes: The FACTOR-64 Randomized Clinical Trial. JAMA 2014;Nov 17:[Epub ahead of print].

Presented by Dr. Joseph B. Muhlestein at the American Heart Association Scientific Sessions, Chicago, IL, November 17, 2014.

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Insulin, Life Style, Cholesterol, LDL, Risk Reduction Behavior, Creatinine, Constriction, Pathologic, Heart Rate, Calcium, Percutaneous Coronary Intervention, Glycated Hemoglobin A, Coronary Angiography, Tomography, Hypersensitivity, Heart Failure, Hypoglycemic Agents, Confidence Intervals, Hospitalization, Diabetes Mellitus, Exercise Test, AHA Annual Scientific Sessions


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