The trial1 randomised 11,140 patients to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy.
Patients had been diagnosed with type II diabetes at 30 years or older and had a history of major cardiovascular disease (stroke, myocardial infarction (MI), hospital admission for transient ischaemic attack or unstable angina, coronary revascularisation, peripheral revascularisation or amputation secondary to vascular disease) or at least one other risk factor for cardiovascular disease. There were no blood pressure criteria for inclusion.
The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or MI, and new or worsening nephropathy or retinopathy.
Over the duration of follow-up (mean duration 4.3 years), blood pressure was reduced by an average of 5.6mmHg systolic and 2.2 mmHg diastolic in patients assigned active treatment compared with those assigned placebo. The relative risk of a major macrovascular or microvascular event was reduced by 9 per cent in the active treatment group (p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant.
The relative risk of death from cardiovascular disease was reduced by 18 per cent and death from any cause was reduced by 14 per cent in the active treatment group.
Significantly fewer total coronary events occurred in patients randomly assigned to active treatment compared with those assigned to placebo. Over five years, one patient in every 75 (95 per cent CI) assigned active treatment would have avoided at least one coronary event. There was no significant difference between randomised groups in either total cerebrovascular events or heart failure.
Active treatment was associated with a significant 21 per cent reduction in all renal events, a borderline significant reduction in new or worsening nephropathy and a significant reduction in the development of microalbuminuria. There was no significant difference between the randomised groups in the rate of new or worsening retinopathy. 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.
The authors concluded that the study findings demonstrate that routine administration of a fixed combination of perindopril and indapamide to patients with type II diabetes reduces the risk of death and major macrovascular and microvascular complications, irrespective of initial blood pressure level or concomitant treatment. They suggest there is a case for considering such treatment routinely for patients with type II diabetes.
1. Patel A, MacMahon S, Chalmers J et al. 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: 370; 829-840.