A randomised trial of routine
blood pressure lowering
among 11140 patients with
type 2 diabetes
Background
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Most people with diabetes will die or be
disabled by vascular complications
Blood pressure levels are a critical
determinant of vascular risk
Treating hypertension in people with
diabetes reduces risk (UKPDS)
Many people with diabetes don’t have
hypertension, but might benefit from
blood pressure lowering
Blood pressure and vascular risk in diabetes
Best evidence: 2000
UKPDS
SBP
UK Prospective Diabetes Study
Blood pressure lowering in diabetes
Unresolved issues: 2000
Among patients with type 2 diabetes,
does routine BP lowering therapy:
ƒ Produce additional benefits when systolic
pressure is lowered below 145 mmHg?
ƒ Produce similar benefits for hypertensive
and non-hypertensive patients?
ƒ Produce benefits additional to those
produced by other treatments, including
ACE inhibitors?
Design features
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Randomised placebo-controlled trial
Fixed combination of perindopril and
indapamide (single tablet once a day)
Primary outcomes: major vascular events
11 140 patients with type 2 diabetes from
20 countries
4.3 years average follow-up
Adherence at end of follow-up
> 73% (active) vs 74% (placebo)
Blood pressure reduction
165
Placebo
Perindopril-Indapamide
Mean Blood Pressure (mmHg)
155
Average BP
during follow-up
Systolic
145
135
140.3 mmHg
134.7 mmHg
∆ 5.6 mmHg (95% CI 5.2-6.0); p<0.001
125
115
105
95
85
Diastolic
75
∆ 2.2 mmHg (95% CI 2.0-2.4); p<0.001
65
R
6
12
18
24
30
36
Follow-up (Months)
42
48
54
60
77.0 mmHg
74.8 mmHg
ADVANCE BP reduction in context:
UK Prospective Diabetes Study
ADV
UKPDS
SBP
UK Prospective Diabetes Study
Main results
Mortality and morbidity
All-cause mortality
Cumulative incidence (%)
10
Placebo
Perindopril-Indapamide
5
Relative risk reduction
14%: 95% CI 2-25%
p=0.025
0
0
6
12
18
24
30
36
Follow-up (months)
42
48
54
60
Deaths
Cardiovascular
5%
Cumulative incidence (%)
Placebo
Perindopril-indapamide
Non-cardiovascular
5%
Placebo
Perindopril-indapamide
Relative risk reduction
18%; p=0.027
6
12 18 24 30 36 42 48 54 60
Follow-up (months)
Relative risk reduction
8%; p=0.41
6
12 18 24 30 36 42 48 54 60
Follow-up (months)
Combined primary outcomes
Major macro or microvascular event
Cumulative incidence (%)
20
Placebo
Perindopril-Indapamide
10
Relative risk reduction
9%: 95% CI: 0 to 17%
p=0.041
0
0
6
12
18
24
30
36
Follow-up (months)
42
48
54
60
Other outcomes
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14% reduction in coronary heart disease
21% reduction in renal disease
For all outcomes, similar benefits:
•
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In those with or without hypertension
In the presence or absence of treatment with:
− ACE inhibitors and other BP lowering drugs
− Statins and other lipid lowering drugs
− Aspirin and other antiplatelet drugs
Very good control of all risk factors in
both groups by the end of follow-up
Blood pressure lowering in diabetes:
unresolved issues 2000
Among patients with type 2 diabetes,
does routine BP lowering therapy:
1. Produce additional benefits when systolic
pressure is lowered below 145 mmHg? YES
2. Produce similar benefits for hypertensive
and non-hypertensive patients? YES
3. Produce benefits additional to those
produced by other treatments, including
ACE inhibitors? YES
Global projections for diabetes (millions)
2007-2025
53.2
64.1
+21%
28.3
40.5
+43%
24.5
44.5
+81%
16.2
32.7
+102%
10.4
18.7
+80%
46.5
80.3
+73%
67.0
99.4
+48%
World
2007 = 246 million
2025 = 380 million
Increase +55%
Diabetes Atlas, 3rd edition, IDF 2006
Potential global benefits of treatment
2010-2015
If the benefits observed in
ADVANCE were applied to just half
the world’s diabetic population
Approximately 1.5 million deaths
could be avoided over this period
Diabetes Atlas, 3rd edition, IDF 2006