Efficacy and safety of fixed combination of perindopril and indapamide in type 2 diabetes: results from ADVANCE in context of available evidence

Objectives The ADVANCE trial was designed to determine the effects of routine blood pressure lowering using a fixed combination of perindopril–indapamide on major vascular outcomes in patients with type 2 diabetes, regardless of initial blood pressure levels or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors. Methods After a 6-week run-in period, 11 140 high-risk individuals with type 2 diabetes were randomized to fixed combination perindopril–indapamide or matching placebo, in addition to current therapy. The two primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately by intention to treat. Results The reduction in blood pressure in participants assigned to active treatment was 5.6/2.2 mmHg greater than that observed in the control group. Active treatment reduced the risk of the combined primary outcome, a major macrovascular or microvascular event by 9% (P = 0.041) and resulted in a 14% (P = 0.025) reduction in all-cause mortality and an 18% (P = 0.027) reduction in cardiovascular mortality. There were reductions of 14% (P = 0.02) in total coronary events and 21% (P < 0.0001) in total renal events. The treatment was well tolerated, with 73% and 74% of patients in the active treatment and placebo groups still adherent to randomized therapy after an average of 4.3 years of follow-up. Conclusions Routine treatment with the fixed combination of perindopril and indapamide was well tolerated and reduced the risk of death and major vascular events, regardless of the initial blood pressure level or concomitant treatments received. The results suggest that for every 79 patients treated in this manner, one death would be avoided over 5 years.