A focus on the ADVANCE and RISC studies in the Diabetes UK conference March 2008
Mar 8, 2008 - 7:21:44 AM
, Reviewed by: Dr. Sanjukta Acharya
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[RxPG] In the recent Annual Professional Conference held in Glasgow(March 5-7, 2008) an interesting talk was on the late breaking trials. There was a focus on the ADVANCE study (presented by Dr Neil Poulter, London) and the RISC study (presented by Dr Mark Walker, Newcastle). Here is a brief overview of the studies and the thoughts of the speakers and audience.
The Advance study which was published in The Lancet, September 2007, has sparked off a lot of discussion this year. As we know the previous UKPDS study had defined a tight systolic BP control as being <140, and this really needed another trial in keeping with recent guidelines like JSB. ADVANCE was a randomised controlled trial done across 20 countries from Asia, Australasia, Europe, and North America. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial was designed to assess the effects on vascular disease of using a fixed combination of the ACE inhibitor, perindopril, and the diuretic, indapamide, in a diverse population of patients with type 2 diabetes and a broad range of blood pressure values. The study also assesses the effects on the same outcomes of an intensive gliclazide MR-based glucose lowering regimen (aiming for a haemoglobin A1C level of 6•5% or lower) compared with standard glucose control.
INCLUSION CRITERIA-Patients were eligible if they had been diagnosed with type 2 diabetes mellitus at the age of 30 years or older and were aged 55 years or older, with a history of major cardiovascular disease or at least one other risk factor for cardiovascular disease. Patients could be normotensive or hypertensive to be included.
METHODS- Patients had an initial run –in period of 6 weeks prior to randomisation when they were given 2 mg perindopril and 0.625 mg of indapamide. Those who were on other ACE inhibitor drugs were switched to perindopril. If the patients tolerated these drugs, then after 6 weeks they were randomly assigned to combined perindopril (2 mg) and indapamide (0•625 mg) or matching placebo for 3 months. Then the doses of randomised therapy were doubled to 4 mg for perindopril and 1•25 mg for indapamide, or matching placebo.
FINDINGS-Over the duration of follow-up, blood pressure was reduced by an average of 5•6 mm Hg systolic and 2•2 mm Hg diastolic in patients assigned active treatment compared to the control. The relative risk reduction for combined macrovascular and microvascular events was 9% in the treated group compared to the placebo group, and similarly the reduction in the macrovascular events risk was 8% and that in the microvascular events was 9%.
DISCUSSION- What was considered significant was the fact that the study failed to show any reduction in the endpoints of stroke and in microvascular eye disease. The stroke rate was thought to be the same in both groups due to the use of calcium channel blockers in the control group. It was put forward as the speaker’s thoughts that the reduction in events may have been due to the Blood pressure lowering, due to the drugs used or due to the RAS blockage via the ACE inhibitors. The recent stoppage of the intensive blood sugar treatment arm in the ACCORD study which was stopped due to increased mortality was also discussed and it was felt that maybe the higher insulin usage and the higher risk population in the ACCORD study may have contributed to those adverse events.
The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study was presented by Mark Walker, Newcastle University, UK. The study was a multicentric, prospective cohort study to establish whether insulin resistance predicts development of cardiovascular disease, to determine genetic and environmental contributions and to develop a method of identifying insulin resistant subjects in clinical practice.
INCLUSION – Patients between the ages of 30-60 years who were not known to have hypertension, diabetes mellitus, dyslipidaemia or established, cardiovascular disease, renal failure, cancer or lung disease.
METHOD – Insulin resistance was measured with a hyperinsulinaemic, euglycaemic clamp. Physical examination, CVD risk assessment, oral glucose tolerance test, measurement of physical activity with an accelerometer and measurement of carotid artery intima media thickness measurement was carried out. There is an initial 3 year and then 10 year follow up.
RESULTS- It was found that the BMI, waist – hip ratio, insulin resistance and insulin exposure independently predicted Cardiometabolic risk factor score. Insulin sensitivity was found to increase with level of activity. Total physical activity was also associated with carotid artery stiffness. The CDKAL and HHEX/IDE susceptibility alleles were associated with impaired pancreatic ß cell function. Only the FTO allele was associated with decreased insulin sensitivity, which was mediated through increased adiposity. Longitudinal data over the complete planned follow-up period is needed to show whether insulin resistance is an independent predictor of the development of atherosclerosis and CVD.
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About Dr. Sanjukta Acharya
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This news story has been reviewed by Dr. Sanjukta Acharya before its publication on RxPG News website. Dr. Sanjukta Acharya, MBBS is the chief editor for RxPG News website. She oversees all the medical news submissions and manages the medicine section of the website. She has a special interest in diabetes and endocrinology.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
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