title: Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk.
  
  
  BACKGROUND
  Despite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking.
  
  
  METHODS
  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. 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.
  
  
  RESULTS
  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; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in "overt or silent CAD progression" of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; 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 7-fold higher rate of progression to "overt or silent CAD," despite therapy. Randomized patients' outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632).
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland. Electronic address: michael.zellweger@usb.ch.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zellweger
authors.affiliation: District Hospital, Schopfheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Maraun
authors.affiliation: District Hospital, Lörrach, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Osterhues
authors.affiliation: Division of Endocrinology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.affiliation: Division of Nuclear Medicine, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Müller-Brand
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Raban
authors.initials: R
authors.lastname: Jeger
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Otmar
authors.initials: O
authors.lastname: Pfister
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Thilo
authors.initials: T
authors.lastname: Burkard
authors.affiliation: Department of Cardiac Surgery, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Eckstein
authors.affiliation: Clinical Trial Unit, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: von Felten
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Osswald
authors.affiliation: Department of Cardiology, University Hospital, University of Basel, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfisterer
mesh_terms: D058070:Asymptomatic Diseases; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000628:therapy; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D010865:Pilot Projects; D015995:Prevalence; D018570:Risk Assessment; D015899:Tomography, Emission-Computed, Single-Photon
keywords: coronary artery disease; diabetes type 2; myocardial perfusion SPECT; risk stratification; silent ischemia; treatment