Detection of Ischemia in Asymptomatic Diabetics - DIAD

Description:

Patients with diabetes mellitus are at high risk for cardiovascular events, and are known to be at high risk for silent ischemia. Earlier studies have demonstrated that inducible ischemia is an independent predictor of adverse diabetic outcomes in diabetic patients. The DIAD study sought to randomize diabetic patients to screening with myocardial perfusion imaging (MPI) or no screening.

Hypothesis:

Systemic screening of asymptomatic diabetic patients would identify high-risk individuals, and reduce their risk of myocardial infarction (MI) or death.

Study Design

Study Design:

Patients Screened: 2,764
Patients Enrolled: 1,123
Mean Follow Up: 5 years
Mean Patient Age: 60.8 years
Female: 47

Patient Populations:

  • Age between 50 and 75 years
  • Onset of diabetes after 30 years of age, with no history of ketoacidosis

Exclusions:

  • Angina pectoris or chest discomfort evaluated with a positive Rose questionnaire
  • Stress test or coronary angiography within the prior 3 years
  • History of MI, heart failure, or coronary revascularization
  • Abnormal rest electrocardiographic results, i.e., pathological Q waves, ischemic (≥1 mm depression) ST segments, deep negative T waves, or complete left bundle branch block
  • Any clinical indication for stress testing
  • Active bronchospasm precluding the use of adenosine
  • Limited life expectancy due to cancer or end-stage renal or liver disease

Primary Endpoints:

Nonfatal MI and cardiac death

Secondary Endpoints:

Unstable angina, heart failure, stroke, and coronary revascularization

Drug/Procedures Used:

Patients were randomized to screening with adenosine Tc-99m sestamibi MPI or to no screening.

Concomitant Medications:

Insulin (10%), oral glycemic agents (64%), lipid-lowering agents (78%), antihypertensive agents (75%), and aspirin (74%)

Principal Findings:

A total of 1,123 patients were randomized, 561 to screening with MPI and 562 to no screening. Baseline characteristics were similar between the two groups. The mean duration of diabetes was 7.0 years, with a mean baseline glycated hemoglobin of 7.0%. Patients in the nonscreening arms were more likely to undergo a nonprotocol stress test (21% vs. 30%, p < 0.001).

The primary outcome of nonfatal MI or death was similar between the screening and no screening arms (2.7% vs. 3.0%, hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.44-1.80, p = 0.73). All-cause mortality rates were similar as well (3.2% vs. 2.7%, p = 0.60). There was no difference in the incidence of unstable angina (0.7% vs. 0.5%, p = 0.70), heart failure (1.2% vs. 1.2%, p = 0.99), or stroke (1.8% vs. 0.9%, p = 0.20). Overall rates of revascularization were similar between the two arms as well (5.5% vs. 7.8%, p = 0.14), including the incidence of percutaneous interventions (2.7% vs. 4.8%, p = 0.74) and coronary artery bypass grafting (2.9% vs. 3.6%, p = 0.76).

The majority of screened patients (78.4%) had normal imaging. In the screened arm, patients with moderate to large MPI defects (6.3%) had a higher risk of nonfatal MI or cardiac mortality (HR 6.3, 95% CI 1.9-20.1, p < 0.05).

Interpretation:

The results of the DIAD trial indicate that screening for silent ischemia with MPI testing in diabetic patients is not associated with a reduction in cardiovascular events, compared with no screening. Moreover, in patients who were screened, only about 6.3% had moderate to severe MPI defects.

The results of the DIAD study are interesting, and together with some recent trials, challenge several paradigms in the primary prevention of coronary artery disease (CAD) in diabetic patients. ACCORD and ADVANCE did not note a reduction in cardiovascular events with tight glycemic control in diabetic patients without known CAD. JPAD and POPADAD did not show a benefit for primary prevention of CAD with aspirin.

On the other hand, patients with diabetes are known to have a higher risk of cardiovascular mortality and morbidity, and diabetes is considered as a CAD equivalent. The optimal strategy for risk stratification and primary prevention of CAD in diabetic patients thus needs further study.

References:

Young LH, Wackers FJ, Chyun DA, et al., on behalf of the DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301:1547-55.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Imaging, Nuclear Imaging

Keywords: Myocardial Perfusion Imaging, Stroke, Myocardial Infarction, Hemoglobin A, Glycosylated, Heart Failure, Ketosis, Confidence Intervals, Coronary Artery Bypass, Diabetes Mellitus, Exercise Test


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