Clinical trial of the month. ADVANCE: improved survival and better vascular and renal outcomes with a fixed combination of perindopril and indapamide in patients with type 2 diabetes

peer reviewedThe controlled ADVANCE trial compared the incidence of major macrovascular and microvascular complications in 5,569 type 2 diabetic patients randomised to a fixed combination of perindopril and indapamide and in 5,571 patients randomised to placebo, followed for a mean duration of 4.3 years. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg, despite the fact physicians were allowed to adjust antihypertensive therapy ad libitum. The relative risk of a major macrovascular and microvascular event (primary endpoint) was reduced by 9% (p = 0.041) in the active group. The separate reductions in macrovascular and microvascular events were similar but were not independently statistically significant. The relative risk of death was significantly reduced by 14% (p = 0.025), essentially due to a lower death rate from cardiovascular diseases (-18%; p = 0.027). The incidence of any coronary event was also significantly reduced (-14 %; p = 0.020), while only a trend was observed for all cerebrovascular events. Finally, renal events were significantly less frequent (-21%; p < 0.0001) whereas all ocular events were only slightly reduced (-5%; NS) in the active group as compared to the placebo group. The fixed combination of perindopril and indapamide was well tolerated and easy to administer. Overall one death due to any cause would be averted among every 79 diabetic patients assigned active therapy for 5 years. There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline