Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial

Patel, A and Mohan, V (2007) Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. The Lancet, 370 (9590). p. 829. ISSN 01406736

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Abstract

Background Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the eff ects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs. Methods The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fi xed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defi ned as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925. Findings After a mean of 4·3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5·6 mm Hg and diastolic blood pressure of 2·2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15·5%] active vs 938 [16·8%] placebo; hazard ratio 0·91, 95% CI 0·83–1·00, p=0·04). The separate reductions in macrovascular and microvascular events were similar but were not independently signifi cant (macrovascular 0·92; 0·81–1·04, p=0·16; microvascular 0·91; 0·80–1·04, p=0·16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3·8%] active vs 257 [4·6%] placebo; 0·82, 0·68–0·98, p=0·03) and death from any cause was reduced by 14% (408 [7·3%] active vs 471 [8·5%] placebo; 0·86, 0·75–0·98, p=0·03). There was no evidence that the eff ects of the study treatment diff ered by initial blood pressure level or concomitant use of other treatments at baseline. Interpretation Routine administration of a fi xed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confi dence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy.

Item Type:Article
Official URL/DOI:http://dx.doi.org/10.1016/S0140-6736(07)61303-8
Uncontrolled Keywords:type 2 diabetes mellitus;macrovascular;the ADVANCE trial
Subjects:Diabetes Clinical Trials
Diabetes Clinical Trials > Controled Trial
Diabetes
Divisions:Department of Diabetology
Department of Clinical Trials
ID Code:471
Deposited By:INVALID USER
Deposited On:15 Feb 2010 09:45
Last Modified:15 Feb 2010 09:45

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