Perindopril/Indapamide Combination Provides Multiple Benefits For Diabetics
Featured ArticleMain Category: Diabetes
Also Included In: Hypertension; Clinical Trials / Drug Trials
Article Date: 03 Sep 2007 - 0:00 PDT
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Antihypertensive therapy involving a fixed combination of the angiotensin-converting enzyme (ACE)-inhibitor perindopril and the diuretic indapamide (Preterax) prolongs survival and decreases the likelihood of coronary and renal events in type 2 diabetics and is also well tolerated, new data show.
The results are from the blood pressure-lowering phase of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and were reported at the European Society of Cardiology Congress 2007 and published online in The Lancet.
The data also showed that the benefits of routine use of the fixed-dose combination occurred irrespective of enrollment blood pressure levels.
"If the benefits seen in ADVANCE were applied to half the population with diabetes worldwide, more than one million deaths would be avoided over five years," co-principal investigator Dr. John Chalmers, with the University of Sydney's George Institute for International Health in Sydney, Australia, said.
His group randomized 11,140 normotensive or hypertensive type 2 diabetics to treatment with either fixed-dose combination of perindopril and indapamide or placebo on top of their current diabetes therapy.
At a mean follow-up of 4.3 years, the relative risk of death from any cause was significantly decreased by 14% and the risk of death from cardiovascular disease by 18%. Combination therapy led to a significant 14% decrease in total coronary events and a 21% decrease in renal events.
Active treatment was also associated with a significant 9% decrease in the relative risk of a major macrovascular or microvascular event. The separate reductions in macrovascular and microvascular events were similar but not significant by themselves.
Overall, the risk of death from diabetes-related complications was reduced by nearly one-fifth with no side effects.
Baseline blood pressure had no effect on treatment outcome.
At the end of the trial, adherence to the active treatment was 73%, and adherence to placebo was 74%.
"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 reduced the risk and 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," Dr. Chalmers pointed out.
Based on the findings, he called for physicians to consider the routine use of the perindopril/indapamide combination in type 2 diabetics.
Currently, there are roughly 250 million diabetics worldwide, and that figure is expected to reach 350 million by the 2030.
The ADVANCE trial was conducted at 215 sites in 20 countries worldwide.
-- European Society of Cardiology Congress 2007
The Lancet
Jill Stein
Jillstein03 at cs.com
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Perindopril & Indapamide: Who Played The Key Role In ADVANCE Trial?
posted by crtzengweb on 24 Oct 2007 at 6:00 amEffects 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.
Lancet. 2007 Sep 8;370(9590):829-40.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView...
ADVANCE trial was done by 215 collaborating centres in 20 countries.
After a 6-week active run-in period, 11140 patients with type 2
diabetes were randomised to treatment with a fixed combination of
perindopril and indapamide or matching placebo, in addition to current
therapy.
It showed significant outcome benefits including all-cause mortality,
CV mortality, etc. To explain the source of outcome benefit in such a successful trial, we found that there was a large BP difference of 5.6/2.2mmHg between active and placebo groups.
In addition to BP lowering, it's reasonable to examine drug component
difference between active and placebo groups retrospectively to
explore the beyond BP effect, if there was any. We knew that the study
drugs were perindopril and indapamide. And we expect there was limited use of these drugs(ACEI&thiazide) in placebo group. When examining placebo group at end of follow-up, 55% of patients used perindopril when only 5% of patients used thiazides. As incomplete controlling of perindopril occured, outcome benefits of perindopril between groups may be halved. In contrast to perindopril, well-controlling of thiazide(indapamide) may reveal nearly full-strength outcome benefit, if there was any.
It seems that indapamide played a greater role than perindopril in
ADVANCE trial, whether positive or negative. And, we didn't know
whether perindopril had a much more greater outcome benefits that even half of them overcame full-strength effects of indapamide.
Perindopril & Indapamide: Who played the key beneficial role in ADVANCE trial?
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