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ADVANCE: action in diabetes and vascular disease

Journal of Human Hypertension volume 19, pages S27–S32 (2005)Cite this article

Abstract

The burden of Type II diabetes is growing rapidly worldwide, across high-, middle- and low-income countries. This burden is associated primarily with increased risks of macrovascular and microvascular diseases, and it is agreed that multifactorial treatment regimens are required to reduce it. ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation) is a large-scale, 2 × 2 factorial, randomised clinical trial. It will investigate the potential benefits of blood pressure lowering, using a fixed low-dose combination of perindopril and indapamide vs placebo, and of tighter glucose control, using an intensive gliclazide-MR-based glucose control regimen vs a standard guidelines-based regimen, separately and together. The two primary outcomes are a composite macrovascular end point of nonfatal stroke, nonfatal myocardial infarction and cardiovascular death; and a composite microvascular end point of new or worsening nephropathy or microvascular eye disease. Following successful recruitment and randomisation of 11 140 participants by March 2003, the study is currently half way through its planned follow-up of 4.5 years. Adherence to randomised study treatment is good; and loss to follow-up is minimal. It is hoped that the study will answer a number of unresolved issues. The blood pressure lowering arm will investigate the possible reduction in major vascular disease in patients with Type II diabetes whether or not they have hypertension, and the possible benefits of blood pressure lowering in such patients already receiving background therapy with the ACE inhibitor perindopril. The glucose control arm will investigate the possible reduction in both macrovascular and microvascular disease achieved with tighter glucose control, targeting an HbA1c of 6.5% and a fasting blood glucose of 6.0 mmol/l. Finally, the factorial design will enable investigation of the combined effects of more intensive glucose control and tighter control of blood pressure.

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Acknowledgements

ADVANCE is an investigator-initiated and conducted study supported by grants from the Institut de Recherches International Servier, and the National Health and Medical Research Council of Australia.

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Authors and Affiliations

  1. The George Institute for International Health, The University of Sydney and The Royal Prince Alfred Hospital, Sydney, NSW, Australia

    A Patel & J Chalmers

  2. Department of Clinical Pharmacology, Cardiovascular Studies Unit, St Mary's Hospital Campus, Imperial College, London, UK

    N Poulter

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  1. A Patel
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  2. J Chalmers
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  3. N Poulter
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Correspondence to J Chalmers.

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Conflict of interest

John Chalmers has received grants from Servier as Co-Principal Investigator for the PROGRESS and ADVANCE trials, administered by the University of Sydney. All three authors have received honoraria from Servier for speaking at scientific meetings.

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Patel, A., Chalmers, J. & Poulter, N. ADVANCE: action in diabetes and vascular disease. J Hum Hypertens 19 (Suppl 1), S27–S32 (2005). https://doi.org/10.1038/sj.jhh.1001890

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