ADVANCE was planned to investigate the effects of routine blood pressure lowering with the fixed combination perindopril–indapamide on major vascular events in people with type 2 diabetes, irrespective of initial blood pressures or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors.
A total of 11 140 individuals with type 2 diabetes were randomly assigned to fixed combination perindopril–indapamide or matching placebo, after a 6-week run-in period. The primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately, by intention to treat.
Active treatment reduced blood pressure by 5.6/2.2 mmHg compared with placebo and the relative risks of all deaths, cardiovascular deaths and major vascular events, by 14% (P = 0.025), 18% (P = 0.027) and 9% (P = 0.041), respectively. There were also reductions in total coronary events (14%; P = 0.02) and total renal events (21%; P < 0.0001). Study treatment was well tolerated, with 73% and 74% of participants who received active treatment and placebo, respectively, still adherent to randomized therapy after an average of 4.3 years of follow-up.
Routine treatment with the fixed combination perindopril–indapamide, on top of all concomitant protective therapies, was well tolerated and reduced the risks of death and vascular disease irrespective of the initial level of blood pressure. The results suggest that for every 79 patients so treated, one death would be averted over 5 years.