Table 1 Description of the studies included in the meta-analysis
Faglia et al. (2005) | DIAD (2009) | DYNAMIT (2011) | FACTOR-64 (2014) | DADDY-D (2015) | |
|---|---|---|---|---|---|
Number of patients | 141 | 1123 | 631 | 899 | 520 |
Design | Randomized | Randomized | Randomized | Randomized | Randomized |
Monocenter | Multicenter | Multicenter | Multicenter | Monocenter | |
Italy | USA and Canada | France | USA | Italy | |
Period of inclusion | July 1998 to July 1999 | July 2000 to August 2002 | December 2000 to June 2003 | July 2007 to May 2013 | September 2007 to May 2012 |
Follow-up | 4.3 years | 5 years | 3.5 years | 4 years | 3.6 years |
Inclusion criteria | - Type 2 DM - 45–75 years - At least 2 of the following: 1. total cholesterol ≥240 mg/dL or HDL-cholesterol ≤35 mg/dL or pharmacological therapy 2. blood pressure >140–90 mmHg or pharmacological therapy 3. active smoking 4. albumin excretion >30 mg/24 h 5. family history of CAD | - Type 2 DM occurring at age 30 years or older with no history of ketoacidosis - 50–75 years | - Type 2 DM - 55–75 years - At least 2 of the following: 1. albumin excretion >30mg/L or >30 mg/24 h 2. treated or untreated hypertension 3. treated or untreated lipid abnormality 4. peripheral arterial disease 5. prior transient ischemic accident 6. smoking 7. family history of CAD | - Type 1 or type 2 DM - Men ≥50 years or women ≥55 years with DM documented for ≥3 years, or men ≥40 years or women ≥45 years with DM documented for ≥5 years - Use of antidiabetic medication for ≥1 year prior to enrollment | - Type 2 DM documented for ≥1 year - 50–70 years - Normal sinus rhythm on ECG - Cardiovascular risk score ≥10 % according to Italian risk chart [11] - Ability to exercise |
Exclusion criteria | - Dialysis - Leg amputation - Poor-prognostic disease | - Angina pectoris or chest discomfort - Stress test or coronary angiography within the prior 3 years - History of MI, heart failure, or coronary revascularization - Abnormal results of rest ECG - 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 | - History of MI, CAD, or stroke - Previous positive stress test or myocardial perfusion imaging - Previous negative stress test or myocardial perfusion imaging within the last 3 years | - Any documented atherosclerotic cardiovascular disease - Treatment with an investigational drug within 30 days - Therapy or condition posing a risk for adherence to study requirements - Pregnancy, lactation, or childbearing potential without effective contraception - Limited life expectancy or comorbidity making primary screening and treatment inappropriate | - Prior CAD or heart failure - ETT or other stress testing or coronary angiography performed within 1 year - ECG showing left bundle branch block or ST depression >1 mm or a Q wave - Glomerular filtration rate <40 ml/min/1.73 m2 - Contraindication to double antiplatelet agent treatment - Life-threatening condition or major psychiatric disorder or active drug abuse |
Screening protocol | ETT and dipyridamole stress echography. | Adenosine Tc-99 m sestamibi myocardial perfusion imaging. | ETT or dipyridamole SPECT in patients unable to perform the exercise test, with a sub-maximal negative exercise test result or with ECG abnormalities impairing the interpretation of the exercise test. | CCTA screening. If the serum creatinine level was 2.0 mg/dL or greater for men or 1.8 mg/dL or greater for women, or if some other contraindication to performing CCTA was present, screening was performed without contrast, and only a CAC score was obtained. | ETT. |
Treatment plan if screening test abnormal | All subjects with ≥1 test positive were advised to undergo coronary angiography. All subjects with positive screening had to undergo cardiological consultation and follow-up. All the subjects with negative screening and the subjects in the control arm did not undergo any cardiological workup in the absence of any cardiac symptoms. | None. The results of the screening test were communicated to the participants and their personal physicians. | None. Subsequent investigations (such as coronary angiography) and treatments (such as revascularization procedures) were left at the cardiologist’s decision. | Based on CCTA results, patients with severe stenosis were recommended to undergo coronary angiography; patients with moderate stenosis were recommended to receive stress cardiac imaging. Standard medical management was recommended to patients of the control group and to patients with normal CCTA. Patients with abnormal CCTA or a CAC score >10 were recommended to begin aggressive care to reduce risk factors [14]. | Coronary angiography was proposed to all patients with positive ETT. |