US_Cardio_Patel_Cardiology_book_temp 26/10/2009 13:08 Page 48
Risk Management
initial BP levels and regardless of use of concomitant therapies than that reported by other studies of more intensive glucose
(including ACE inhibitors, statins, and aspirin).
1
lowering.
3–5
In addition, there was no increase in mean bodyweight
among patients randomized to intensive glucose control, but a small
In the glucose-lowering arm, the mean entry HbA
1c
of participants reduction in mean bodyweight among those allocated to standard
was 7.5%, with 91% already receiving oral hypoglycemic agents.
2
By glucose control, so the mean bodyweight of the participants in the
the end of follow-up of those in the intensive control group and intensive arm was 0.7kg higher than in the standard care arm at the end
standard care group, respectively, 92 and 59% were receiving of follow-up (p<0.001).
2
No increase in death was observed with
sulfonylurea, 74 and 67% metformin, 40 and 24% insulin, and 17 and intensive glucose control compared with standard glucose control.
2
11% thiazolidinediones. Intensive glucose control resulted in a mean
HbA
1c
of 6.5%, compared with 7.3% in the standard arm, to produce Treatment of Blood Pressure in
an average difference during follow-up of 0.7% between the groups Type 2 Diabetes
(see Figure 3).
2
In addition, the target HbA
1c
of 6.5% or less was BP is a particularly important determinant of the risk for
achieved by 65% of those assigned intensive glucose control macrovascular and microvascular complications in patients with type
compared with 29% of those assigned standard care. Intensive 2 diabetes.
6,7
In observational analyses, systolic BP levels have been
glucose control reduced the incidence of combined major shown to be linearly associated with the risks for myocardial
macrovascular and microvascular events by 10% (95% CI 2–18; infarction and microvascular events.
8
Although the strength of the
association appears to attenuate somewhat with age, BP remains a
leading determinant of risk in both older and younger individuals.
9
The
effectiveness of BP lowering in patients with type 2 diabetes has been
In observational analyses,
consistently observed in trials of individuals with hypertension.
10–15
systolic blood pressure levels have been
Current treatment guidelines recommend aiming for a target BP level
of 130/80mmHg or lower, with initial therapy including an ACE
shown to be linearly associated with
inhibitor or an angiotensin receptor blocker.
16
However, observational
the risks for myocardial infarction
data demonstrating a continuous association between BP and
cardiovascular risk have been largely ignored despite suggesting
and microvascular events.
potential benefits of BP lowering for a broader range of people with
diabetes. In addition, the relative benefits of specific therapeutic
regimens continue to be debated. The recently published results of
p=0.01). This was primarily due to a significant 21% reduction in the the ADVANCE trial are therefore highly relevant to these important
incidence of new or worsening nephropathy. There were no clinical questions.
significant effects of intensive glucose control on major
macrovascular events (relative risk reduction [RRR)] 6%, 95% CI -6 to The BP-lowering arm of the trial indicated that, regardless of initial BP
16; p=0.32) (see Figure 2), cardiovascular mortality (RRR 12%, 95% CI level, the presence or absence of hypertension and any other
-4 to 26; p=0.12), or all-cause mortality (RRR 7%, 95% CI -6 to 17; treatment being taken, routine administration of the fixed
p=0.28).
2
The treatment effects were consistent across a range of combination of perindopril and indapamide to individuals with type 2
participant subgroups defined by major baseline characteristics, diabetes was well tolerated and reduced the risks for death and major
including duration of diabetes and prior history of macrovascular or vascular events.
1
In addition, the results suggested that treatment
microvascular disease (p>0.1 for heterogeneity for all comparisons).
2
with a single tablet of perindopril–indapamide once daily would
prevent one major vascular event among every 66 patients, one death
Safety and Tolerability of the among every 79 patients, one coronary event among every 75
ADVANCE Trial Interventions patients, and one renal event among every 20 patients treated for five
The fixed combination of perindopril and indapamide was well years.
1
From a global perspective, if only half of all patients with type
tolerated. At the end of follow-up, 73 and 74% of patients in the active 2 diabetes were to be treated with the fixed combination of
treatment and placebo groups, respectively, remained adherent to perindopril and indapamide over five years, over 1.5 million deaths
their randomized treatment.
1
Serious suspected adverse drug would be prevented. The trial thus highlighted the potential benefits
reactions leading to discontinuation were reported in 47 patients of an alternative effective strategy for delivering a BP-lowering
(0.8%) on active treatment and 31 patients (0.6%) on placebo. These treatment to patients with a broader range of BPs, including those
included 14 cases of hyperkalemia (six active, eight placebo), two with ‘normal’ BP, and a strategy that would also be applicable to the
cases of hypokalemia (two active), and five cases of hyponatremia vast majority of patients who fail to reach recommended BP targets.
(four active, one placebo). There were also five non-fatal cases of
angioedema (three active, two placebo).
1
Treatment of Glucose Levels in
Type 2 Diabetes
As expected, in the glucose control arm severe hypoglycemia was more Epidemiological studies have also demonstrated a strong relationship
frequent with intensive glucose control (0.7 cases per 100 patient-years) between the level of glycemic control (HbA
1c
) and risks for
than standard care (0.4 cases per 100 patient-years).
2
However, the macrovascular and microvascular complications in people with type 2
overall incidence of severe hypoglycemia in ADVANCE was much less diabetes. In the UK Prospective Diabetes Study (UKPDS) of newly
48 US CARDIOLOGY
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