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