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Diabetes and Cardiovascular Risk
11% thiazolidinediones. Intensive glucose control resulted in a mean type 2 diabetes.
6,7
In observational analyses, systolic BP levels have
HbA
1c
of 6.5%, compared with 7.3% in the standard arm, to produce an been shown to be linearly associated with the risks of myocardial
average difference during follow-up of 0.7% between the groups (see infarction and microvascular events.
8
Although the strength of the
Figure 3).
2
In addition, the target HbA
1c
of 6.5% or less was achieved by association appears to attenuate somewhat with age, BP remains a
65% of those assigned intensive glucose control, compared with 29% leading determinant of risk in both older and younger individuals.
9
of those assigned standard care. Intensive glucose control reduced the The effectiveness of BP lowering in patients with type 2 diabetes
incidence of combined major macrovascular and microvascular has been consistently observed in trials of individuals with
hypertension.
10–15
Current treatment guidelines recommend aiming
for a target BP level of 130/80mmHg or lower, with initial therapy
As expected, in the glucose control arm
including an ACE inhibitor or an angiotensin receptor blocker.
16
However, observational data demonstrating a continuous
severe hypoglycaemia was more frequent
association between BP and cardiovascular risk have been largely
with intensive glucose control (0.7 cases
ignored despite suggesting potential benefits of BP lowering for a
broader range of people with diabetes. In addition, the relative
per 100 patient-years) than with standard
benefits of specific therapeutic regimens continue to be debated.
care (0.4 cases per 100 patient-years).
The recently published results of the ADVANCE trial are therefore
highly relevant to these important clinical questions.
events by 10% (95% CI 2–18; p=0.01). This was primarily due to a The BP-lowering arm of the trial indicated that, regardless of initial
significant 21% reduction in the incidence of new or worsening BP level, the presence or absence of hypertension and any other
nephropathy. There were no significant effects of intensive glucose treatment being taken, routine administration of the fixed
control on major macrovascular events (relative risk reduction [RRR)] combination of perindopril and indapamide to individuals with type
6%, 95% CI -6 to 16; p=0.32) (see Figure 2), cardiovascular mortality 2 diabetes was well tolerated and reduced the risk of death and
(RRR 12%, 95% CI -4 to 26; p=0.12) or all-cause mortality (RRR 7%, 95% major vascular events.
1
In addition, the results suggested that
CI -6 to 17; p=0.28).
2
The treatment effects were consistent across a treatment with a single tablet of perindopril–indapamide once daily
range of participant subgroups defined by key baseline characteristics, would prevent one major vascular event among every 66 patients,
including duration of diabetes and prior history of macrovascular or one death among every 79 patients, one coronary event among
microvascular disease (p>0.1 for heterogeneity for all comparisons).
2
every 75 patients and one renal event among every 20 patients
treated for five years.
1
From a global perspective, if only half of all
Safety and Tolerability of the patients with type 2 diabetes were to be treated with the fixed
ADVANCE Trial Interventions combination of perindopril and indapamide over five years, over
The fixed combination of perindopril and indapamide was well 1.5 million deaths would be prevented. The trial thus highlighted the
tolerated. At the end of follow-up, 73 and 74% of patients in the potential benefits of an alternative effective strategy for delivering
active treatment and placebo groups, respectively, remained a BP-lowering treatment to patients with a broader range of BPs,
adherent to their randomised treatment.
1
Serious suspected including those with ‘normal’ BP, and a strategy that would also be
adverse drug reactions leading to discontinuation were reported in applicable to the vast majority of patients who fail to reach
47 (0.8%) of patients on active treatment and 31 (0.6%) of patients recommended BP targets.
on placebo. These included 14 cases of hyperkalaemia (six active,
eight placebo), two cases of hypokalaemia (two active) and five Treatment of Glucose Levels in
cases of hyponatraemia (four active, one placebo). There were also Type 2 Diabetes
five non-fatal cases of angioedema (three active, two placebo).
1
Epidemiological studies have also demonstrated a strong
relationship between the level of glycaemic control (HbA
1c
) and risks
As expected, in the glucose control arm severe hypoglycaemia was of macrovascular and microvascular complications in people with
more frequent with intensive glucose control (0.7 cases per 100
patient-years) than with standard care (0.4 cases per 100 patient-
years).
2
However, the overall incidence of severe hypoglycaemia in
ADVANCE was much less than that reported by other studies of
The overall incidence of severe
more intensive glucose lowering.
3–5
In addition, there was no
hypoglycaemia in ADVANCE was much
increase in mean bodyweight among patients randomised to
intensive glucose control, but a small reduction in mean
less than that reported by other studies
bodyweight among those allocated to standard glucose control, so
of more intensive glucose lowering.
the mean bodyweight of the participants in the intensive arm was
0.7kg higher than in the standard care arm at the end of follow-up
(p<0.001).
2
No increase in death was observed with intensive
glucose control compared with standard glucose control.
2
type 2 diabetes. In the United Kingdom Prospective Diabetes Study
(UKPDS) of newly diagnosed individuals with type 2 diabetes, for
Treatment of Blood Pressure in example, each 1% higher level of mean HbA
1c
level was associated
Type 2 Diabetes with an approximate 14% greater risk of all-cause death, 14%
BP is a particularly important determinant of the risk of greater risk of myocardial infarction and 37% greater risk of
macrovascular and microvascular complications in patients with microvascular disease.
17
Tight glucose control in the UKPDS was also
44 EUROPEAN ENDOCRINOLOGY