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Cardiovascular Risk in Type 2 Diabetes – Reflecting on the ADVANCE Study
Figure 1: Blood Pressure Figure 3: Glycaemic Control
165
10.0
Average BP
155
during follow-up 9.5
Systolic
145
140.3mmHg 9.0
135
134.7mmHg
8.5
Mean HbA
1c
Δ 5.6mmHg (95% CI 5.2–6.0); p<0.001
125
at final visit
(%)
1c
8.0
115
7.5
105
7.3%
7.0
95
Mean HbA
Δ 0.67% (95% CI 0.64–0.70); p<0.001
6.5 6.5%
85
Diastolic 6.0
Mean blood pressure (mmHg)
75
77.0mmHg
74.8mmHg
Δ 2.2mmHg (95% CI 2.0–2.4); p<0.001
65
5.5
R612 18 24 30 36 42 48 54 60 5.0
Follow-up (months)
0612 18 24 30 36 42 48 54 60 66
Placebo Follow-up (months)
Perindopril/indapamide Standard
Intensive
Mean systolic and diastolic blood pressure during run-in on active treatment and after
Glycaemic control at baseline and during follow-up, according to glucose control strategy, inrandomisation to active treatment or placebo in the blood pressure lowering arm of the
21
the ADVANCE trial.ADVANCE trial.
Figure 2: Key Results from the ADVANCE Trial
Effects of Blood Pressure Lowering (ΔBP = 5.6/2.2mmHg)
Number of Events
Per/Ind Placebo Favours Favours Relative Risk
(n=5,569) (n=5,571) Per/Ind Placebo Reduction (95% CI)
Primary End-points
Combined macro + micro 861 938 9% (0 to 17)
Macrovascular events 480 520 8% (-4 to 19)
Microvascular events 439 477 9% (-4 to 20)
Mortality
All-cause death 408 471 14% (2 to 25)
Cardiovascular death 211 257 18% (2 to 32)
Renal End-points
New/worsening nephropathy 181 216 18% (-1 to 32)
New microalbuminuria 1,094 1,317 21% (14 to 27)
New macroalbuminuria 114 163 31% (12 to 46)
0.5 1.0 2.0
Hazard ratio
Effects of Blood Glucose Lowering (ΔHbA
1c
= 0.7%)
Number of Events
Intensive Standard Favours Favours Relative Risk
(n=5,569) (n=5,571) Intensive Standard Reduction (95% CI)
Primary End-points
Combined macro + micro 1,009 1,116 10% (2 to 18)
Macrovascular events 557 590 6% (-6 to 16)
Microvascular events 526 605 14% (3 to 23)
Mortality
All-cause death 498 533 7% (-6 to 17)
Cardiovascular death 253 289 12% (-4 to 26)
Renal End-points
New/worsening nephropathy 230 292 21% (7 to 34)
New microalbuminuria 1,318 1,434 9% (2 to 15)
New macroalbuminuria 114 163 31% (13 to 45)
0.5 1.0 2.0
Hazard ratio
Per/Ind = perindopril/indapamide.
evidence of heterogeneity in treatment effect in subgroups of In the glucose-lowering arm, the mean entry HbA
1c
of participants
participants defined by key baseline characteristics. In particular, was 7.5%, with 91% already receiving oral hypoglycaemic agents.
2
By
the effects of the treatment were similar across a range of initial BP the end of follow-up of those in the intensive control group and
levels and regardless of use of concomitant therapies (including standard care group, respectively, 92 and 59% were receiving
ACE inhibitors, statins and aspirin).
1
sulphonylurea, 74 and 67% metformin, 40 and 24% insulin and 17 and
EUROPEAN ENDOCRINOLOGY 43
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