ADVANCE study (combination of an angiotensin converting enzyme inhibitor (ACEI) and a diuretic on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus)
ADVANCE study examined the effect of a fixed dose combination of an angiotensin converting enzyme inhibitor (ACEI) and a diuretic on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus
in the ADVANCE study the combination showed some benefits over placebo
RCT of 11,140 patients aged 55 years and older with type 2 diabetes
patients also had either a history of CV disease (including stroke and MI) or at least one other CV risk factor (e.g. age >= 65 years, smoking, history of major microvascular disease)
active treatment with a combination of perindopril and indapamide (initially 2mg/0.625mg, doubled to 4mg/1.25mg after 3 months) was compared with placebo
while taking the combination during the run-in phase, 1,737 other recruited patients withdrew, at least 29% of these due to adverse effects
primary endpoints were composites of major macrovascular events (death from CV disease, non-fatal stroke or non-fatal MI) and major microvascular events (new or worsening renal disease or new or worsening diabetic eye disease)
after 4.3 years, the combined endpoint of major macrovascular and microvascular events was reduced by 1.3% (number needed to treat [NNT]=77; relative risk reduction [RRR] 9%, 95%CI 0% to 17%; P=0.04)
death from CV disease was significantly reduced by 0.8% (NNT=125 over 4.3 years; RRR 18%, 95%CI 2% to 32%; P=0.03) and death from any cause was reduced by 1.2% (NNT= 83; RRR 14, 95%CI 2% to 25%; P=0.03)
significance of study
authors of the paper conclude that, “routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death”
however:
mean blood pressure in patients in the active arm was 5.6/2.2mmHg lower than that in patients in the placebo arm and this was highly statistically significant (p<0.0001)
therefore possible that the differences observed were an effect of lower blood pressure rather than any drug specific action
study adds to the body of evidence that lowering blood pressure in patients with type 2 diabetes reduces CV complications and deaths
also "..based on their safety, efficacy, tolerability and cost, thiazide diuretics are a good first choice agent for most people, including those with type 2 diabetes.." (2)
Reference:
(1) ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial). Lancet 2007;370:829-40.
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