ADVANCE - Blood Pressure Lowering in Patients With Type 2 Diabetes
The results of the blood pressure lowering arm of the ADVANCE (Action in Diabetes and Vascular Disease) study, the largest ever trial conducted in people with type 2 diabetes, were recently reported in the Lancet.
The main finding was that the routine administration of blood pressure lowering with a perindopril/indapamide (4.0mg/1.25mg) combination produced significant reductions in major vascular events and mortality amongst patients with diabetes. Specifically, treatment reduced the combination of major macrovascular (mainly heart disease) and microvascular events (mainly kidney disease) by 9% (p=0.041), the risk of death from any cause by 14% (p=0.025) and the risk of death from cardiovascular causes by 18% (p=0.027). The effects on vascular events included a significant 14% reduction in coronary events, and a significant 21% reduction in renal events.
There are three aspects of the result that are worth particular consideration. First, ADVANCE was not a “hypertension” trial – there were no blood pressure criteria for study eligibility and the treatment was similarly effective in people with and without hypertension. Second, ADVANCE was a pragmatic trial – the perindopril-indapamide combination was administered as a single daily tablet without titration to a blood pressure target. Its effects were evaluated on top of a background of care selected at the discretion of the responsible doctor and reflective of usual practice in each of the 20 countries involved. This included substantial use of other preventative treatments of known benefit (including ACE inhibitors, antiplatelet drugs and statin therapy) with good control of other risk factors (average HbA1c was 6.9% and average LDL cholesterol was 2.7mmol/L at the end of follow-up). The ADVANCE trial provided clear evidence that the perindopril-indapamide treatment was effective on top of these other therapies which are widely used in the European clinical setting. Finally, the study treatment was very well tolerated. ADVANCE participants were given a six week run-in period on perindopril-indapamide prior to starting the study but if they tolerated this (and 87% did) then discontinuation of treatment because of intolerance was very uncommon during the subsequent four years. Average adherence at the end of the follow-up period was almost identical in the active treatment and placebo groups.
This trial provides a very firm basis for the uptake of this intervention strategy in the European setting and it is anticipated that national and international guidelines will be modified to accommodate the study findings. Most patients with type 2 diabetes would be expected to benefit from this therapy with health gains anticipated irrespective of initial blood pressure levels, across a broad range of patient types, and on top of other current treatments. With rates of diabetes in the European Union growing at an alarming rate this study has significant implications for the avoidance or delay of much serious morbidity and mortality. A second component of the ADVANCE trial evaluating the role of intensive glucose control strategies will be reported next year. Hopefully this will bring similarly good news for the prevention of serious vascular complications of diabetes.
30.10.2007
