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Diabetes and Cardiovascular Risk
Cardiovascular Risk in Type 2 Diabetes—Reflecting on the ADVANCE Study
Sophia Zoungas, MD, PhD,
1
John Chalmers, MD, PhD
2
and Anushka Patel, MD, PhD
3
1. Senior Research Fellow, Cardiovascular and Renal Divisions, The George Institute for International Health, University of Sydney, and
School of Public Health, Monash University, Melbourne; 2. Director, Professorial Unit, The George Institute for International Health, University of Sydney;
3. Director, Cardiovascular Division, The George Institute for International Health, University of Sydney
Abstract
The world is facing an unprecedented increase in type 2 diabetes. Most disability and premature mortality experienced by patients with
diabetes is related to vascular disease and, in particular, macrovascular disease (such as coronary heart disease and stroke) and
microvascular disease (such as retinopathy, nephropathy, and neuropathy). Indeed, around 1.9 million cardiovascular deaths worldwide are
attributable to high blood glucose levels and diabetes, as well as to their associated dangerous companions of high blood pressure and
abnormal lipid levels. The global economic costs of diabetes, including foregone economic growth and increasing healthcare expenditure, are
substantial and are anticipated to grow. Therefore, strategies to reduce disease burden have continued to focus on reducing cardiovascular
risk. Recently, a number of large-scale clinical trials have evaluated approaches for managing cardiovascular risk in patients with type 2
diabetes. Among them the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN MR Controlled Evaluation (ADVANCE) trial has
reported the effects of blood pressure lowering and intensive glucose control on major vascular events in patients with established type 2
diabetes. In this article we summarise the findings of the ADVANCE trial and discuss its relevance to the management of cardiovascular risk
in patients with type 2 diabetes worldwide.
Keywords
Type 2 diabetes, cardiovascular risk, mortality, complications, blood pressure treatment, glycemic control, clinical trials
Disclosure: The authors have received lecturing fees from Servier. John Chalmers, MD, PhD, holds a research grant from Servier as principal investigator for ADVANCE. Sophia
Zoungas, MD, PhD, is supported by a National Health and Medical Research Council of Australia Health Professional Research Fellowship. Anushka Patel, MD, PhD, is supported by a
National Heart Foundation of Australia Career Development award.
Received: 27 April 2009 Accepted: 16 July 2009
Correspondence: Sophia Zoungas, MD, PhD, Cardiovascular Division, The George Institute for International Health, University of Sydney, PO Box M201, Missenden Road, Sydney,
NSW 2050, Australia. E: szoungas@george.org.au
Summary of the ADVANCE Trial Findings guidelines-based glucose control were permitted to use sulfonylureas
The ADVANCE trial was a factorial, randomized study of 11,140 (other than gliclazide) and any other available glucose-lowering
individuals with type 2 diabetes from over 200 collaborating centres therapy, including insulin. The primary outcomes were composites of
in 20 countries from Asia, Australasia, Europe, and North America. major macrovascular (non-fatal acute myocardial infarction, non-fatal
Participants with either a history of macrovascular or microvascular stroke, and cardiovascular death) and major microvascular events
disease or at least one major risk factor for cardiovascular disease (new or worsening nephropathy and microvascular eye disease),
and any initial level of blood pressure (BP) and blood glucose were analyzed jointly and separately. The average duration of follow-up was
randomly assigned to the fixed combination of the angiotensin- 4.3 years for the BP-lowering intervention and five years for the
converting enzyme (ACE) inhibitor perindopril and the thiazide glucose control intervention.
1,2
diuretic indapamide (4/1.25mg) or matching placebo and to intensive
glucose control or standard guideline-based glucose control.
1,2
The In the BP-lowering arm of the study, the mean entry BP of participants
glucose-lowering regimen for those randomized to intensive glucose was 145/81mmHg, with over 40% recording a BP below 140/90mmHg.
1
control was based on the modified-release sulfonylurea gliclazide-MR Over the duration of active treatment, BP was reduced by a mean of
30–120mg daily. However, non-pharmacological approaches, other 5.6/2.2mmHg compared with placebo. At the end of follow-up the mean
oral agents, and insulin were recommended to be added as required BP achieved was 134.7/74.8mmHg in the active treatment group and
to achieve the target glycated hemoglobin (HbA
1c
) level of ≤6.5%.
2
140.3/77.0mmHg in the placebo group (see Figure 1).
1
Active treatment
The choice of additional treatments was left to the discretion of the reduced the risk for the combined composite primary outcome of
responsible physician. Participants randomized to standard macrovascular and microvascular events by 9% (95% confidence
© TOUCH BRIEFINGS 2009 95
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