Progression to Overt or Silent Coronary Artery Disease in Asymptomatic Patients With Diabetes Mellitus at High Coronary Risk: Main Findings of the Prospective Multicenter BARDOT Trial With a Pilot Randomized Treatment Substudy

Study Questions:

What is the prevalence of silent and symptomatic progression and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes mellitus (DM) at high coronary risk, and how does treatment of ischemia impact outcome?

Methods:

BARDOT (Basel Asymptomatic High-Risk Diabetics’ Outcome Trial) was a prospective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk documented by peripheral or carotid occlusive disease, retinopathy, microalbuminuria, autonomic cardiac neuropathy, or by the composite of age older than 55 years, diabetes duration longer than 5 years, and two cardiac risk factors (smoking, hypertension, hypercholesterolemia, or positive family history of CAD) in addition to diabetes. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management. The primary endpoint was major adverse cardiovascular events (MACE) defined as “symptomatic” CAD progression including cardiac death, myocardial infarction, and symptom-driven revascularization. The other main endpoint was silent progression defined as new MPS evidence of significant ischemia or scar.

Results:

Mean age was 64 years. An abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio, 3.44; p = 0.011) and ischemia or new scar (34.2%; odds ratio, 15.91; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio, 11.53; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001).

Conclusions:

High-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a sevenfold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patient outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone.

Perspective:

Routine stress imaging is not indicated in type 2 DM because of inadequate yield. This study was conducted in a ‘high risk’ cohort with a very broad definition, and tends to support stress imaging in this group. I think the data should be used to generate an imaging-based randomized trial with a tighter definition of high risk that does not include clinical disease in other vascular beds or is adequately powered for both groups.

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Prevention, Homozygous Familial Hypercholesterolemia, Computed Tomography, Nuclear Imaging, Hypertension, Smoking

Keywords: Myocardial Infarction, Cicatrix, Tomography, Emission-Computed, Single-Photon, Risk Factors, Hypercholesterolemia, Hypertension, Diabetes Mellitus, Smoking


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