Perindopril & Indapamide: Who played the key role in ADVANCE trial?

ADVANCE: Lancet. 2007 Sep 8;370(9590):829-40. PMID:17765963

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 would 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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