A cheap blood pressure tablet could save lives if taken by all people with type 2 diabetes, The Daily Telegraph reported. The newspaper stated that the results could “have implications for the treatment of type 2 diabetes and significantly reduce the risk of heart disease, the biggest killer of diabetics”. It went on to estimate that this would result in saving 22,500 lives over five years by preventing death from heart-related problems and kidney failure.
The research behind these stories is a large randomised controlled trial in people with type 2 diabetes. The research provides good evidence that routine blood pressure lowering, regardless of initial blood pressure, could save lives.
Where did the story come from?
The lead investigators of study are based at the University of Sydney. The study, known as the ADVANCE study, is ongoing and is being conducted by a large collaborative research group including professionals from 20 countries. This set of results was published in the peer-reviewed medical journal, The Lancet.
What kind of scientific study was this?
The study is a large, multi-national, randomised controlled trial set up to investigate blood glucose and blood pressure management in people with type 2 diabetes.
More than 11,000 people were recruited from across 20 countries (across Asia, Australasia, Europe, and North America) and were randomised to receive either a combination of an ACE inhibitor – a drug often used in the treatment of hypertension and heart failure – combined with a diuretic or a placebo. They were then randomised to either an intensive glucose-lowering treatment or to usual glucose-lowering therapy.
The researchers followed up the individuals for an average of 4.3 years; in that time they collected information on any complications that occurred (stroke, heart attack, eye and kidney disease) and any causes of death. The researchers compared the treatment and placebo groups. This particular paper provides results of the comparison between routine blood pressure lowering and placebo. The results of the comparison of intensive glucose-lowering and placebo will be available only after December 2007.
What were the results of the study?
The researchers found that treatment with the combination ACE inhibitor and diuretic reduced blood pressure and, when considered as a combined outcome, reduced the risk of a major micro- or macro-vascular event (eye disease, kidney disease, stroke, heart attack). The researchers also found that the risk of death from cardiovascular disease was reduced by 18% with the treatment and death by any cause was reduced by 14%. There was no difference between the groups in deaths due to non-cardiovascular causes.
What interpretations did the researchers draw from these results?
The researchers concluded that the routine administration of a fixed combination of an ACE inhibitor, which lowers blood pressure, and diuretic is safe and reduced the risk of major vascular events, including death, in people who have type 2 diabetes. Although the majority of participants were also taking other blood pressure lowering treatments during the study, the researchers report that the effects of the particular combination treatment seems to be independent of the use of other treatments, therefore the routine use of this treatment offers further benefits.
What does the NHS Knowledge Service make of this study?
This is a large, well-conducted randomised controlled trial which provides sound evidence of benefits in routine treatment with a combination of an ACE inhibitor and diuretic for people with type 2 diabetes:
- The two groups of people in the study (treatment and placebo groups) were well-balanced at the start; this is an important feature of a well-conducted study as it ensures that real treatment effects can be seen at the end of the study.
- The researchers did further analyses to see whether a person’s blood pressure at the start of the study affected the benefits they received from this treatment; they found that the combination benefited everyone, regardless of whether they were hypertensive at the start.
- The ‘relative’ risk reduction of 18% for cardiovascular deaths represents an ‘absolute’ difference of 46 cardiovascular deaths over about 4 years. This means that, of the 5,570 people taking the treatment, 211 people died compared to 257 deaths in the 5,570 people taking the placebo. The reduction in risk should be considered in light of the fact that the event rate (i.e. total number of people dying from a cardiovascular cause) was quite low.
- Some people develop a cough when starting an ACE inhibitor and the low rate of cough in the intervention group (3.3%) may be surprising. However almost 43% of people in this group were already taking an ACE-inhibitor before the trial began and were first changed to perindopril (the study ACE inhibitor) and then randomised to the placebo tablet or the higher dose of perindopril. The low rates of adverse effects in this study may not be observed when the combination drug is used as first line in patients with diabetes.
This international study adds further weight to the argument that lowering blood pressure is important for people at increased risk of heart disease and stroke. A fixed dose combination pill given to all people with diabetes, irrespective of their blood pressure, may be an acceptable way to do this.