By 2030, an estimated 350 million people will be living with diabetes worldwide. Individuals with type 2 diabetes are at an increased risk of cardiovascular outcomes including heart attack, stroke, and microvascular outcomes such as degenerative eye disease. Current guidelines recommend the lowering of blood pressure for people with type 2 diabetes to reduce the risk of such events, though a strategy to reduce blood pressure regardless of baseline blood pressure (ie, including people with diabetes who do not have raised blood pressure) has not been proven in randomised trials to date.
The ADVANCE trial recruited around 11000 individuals with type 2 diabetes from 215 medical centres in 20 countries across the world. Individuals were randomised to receive either a combination of the ACE inhibitor perindopril and the diuretic indapamide or placebo and were followed up for over four years.
Individuals given active therapy had an average reduction in systolic blood pressure of 5•6 mm Hg and diastolic blood pressure of 2•2 mm Hg compared with the placebo group. The relative risk of a major macrovascular or microvascular event was reduced by 9% (15•5% active vs 16•8% placebo). The separate reductions in macrovascular and microvascular events were similar but were not statistically significant by themselves.
The relative risk of death from cardiovascular disease was reduced by 18% (3•8% active vs 4•6% placebo), and death from any cause was reduced by 14% (7•3% active vs 8•5% placebo). The results were not dependent on baseline blood pressure or whether individuals were using other treatments for diabetes.
One of the authors, John Chalmers (The George Institute, University of Sydney, Australia), comments: “In summary, the results of ADVANCE indicate that the routine administration of a fixed combination of perindopril and indapamide to a broad range of patients with diabetes reduces the risks of death and major macrovascular or microvascular complications, irrespective of initial blood pressure level or ancillary treatment with the many other preventive treatments typically provided to diabetic patients today. The study treatment was well tolerated, needed little monitoring or titration and is, therefore, suitable for use in a wide range of clinical circumstances worldwide. If the benefits seen in ADVANCE were applied to just half the population with diabetes worldwide, more than a million deaths would be avoided over 5 years. For these reasons, there is now a case for considering such treatment routinely for patients with type 2 diabetes.”
In an accompanying Comment, Norman M Kaplan (University of Texas Southwestern Medical Center, USA) cautions against over-interpretation of ADVANCE. He concludes: “The fixed combination of perindopril and indapamide could be the best possible protector against hypertension-related consequences for patients with type 2 diabetes, but I believe that other drugs—if they lower blood pressure as much and do not have metabolic side-effects—would be as protective as this combination treatment. As has been said many times by many experts: in most circumstances, lowering the blood pressure is what counts, not the way by which it is lowered.”
Dr John Chalmers, c/o Emma Orpilla, +61 410 411983; alternative contact +61 405 196000; +61 410 553800.
Professor Norman M Kaplan, Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; T) +1 214 648 2103; Norman.Kaplan@UTSouthwestern.edu
Notes to Editors:
*The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE)
** Results of ADVANCE are being presented at a Hotline presentation at the European Society of Cardiology meeting from 1118-1131 Sunday Sept 2, 2007.
Journal
The Lancet