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.
Lancet. 2007 Sep 8;370(9590):829-40.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSear
ch=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 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 plays the key beneficial role in ADVANCE
trial?
What do you think about it?