Title: Blood Pressure Lowering Treatment Trialists Collaboration Second cycle of overview analyses
1Blood Pressure Lowering Treatment Trialists
CollaborationSecond cycle of overview analyses
2Overview
- Background and aims
- Methods
- Summary of first cycle analyses
- Findings of second cycle analyses
- Interpretation
3Background
- Established in 1995 by the principal
investigators of ongoing large-scale trials - To more reliably determine the effects of various
blood pressure lowering regimens on major
vascular outcomes and death - First cycle of analyses published Lancet 2000
355 1955-64
4Aims
To compare the effects on mortality and major
morbidity of
- Newer blood pressure lowering agents versus
placebo - More intensive versus less intensive blood
pressure lowering regimens - Blood pressure lowering regimens based on
different drug classes
5Pre-specified trial eligibility criteria
- Random allocation to
- blood pressure lowering agent versus placebo
- different blood pressure goals
- different blood pressure lowering drugs
- At least 1,000 patients years of follow-up per
randomised group planned - Results not available before July 1995
6Pre-specified outcomes
- Primary outcomes
- Stroke
- Coronary heart disease
- Heart failure (fatal or hospitalised)
- Total cardiovascular events (composite of all
above) - Cardiovascular mortality
- Total mortality
7Statistical methods
- Analyses by intention-to-treat
- Relative risks combined using fixed effects model
- Each study weighted by inverse of variance
- Overall relative risks and 95 CI calculated
- Chi square tests of homogeneity
8Contributing trials
Second cycle (29 trials, n 162,341)
IDNT INSIGHT JMIC-B LIFE NICOLE NICS-EH NORDIL PAR
T-2 PREVENT PROGRESS
QUIET RENAAL SCAT SCOPE SHELL STOP-2 SYST-EUR UKPD
S-HDS VHAS
AASK ABCD (H) ABCD (N) ALLHAT ANBP2 CAPPP CONVINC
E ELSA HOPE HOT
9ACE inhibitor vs. placebo
10Calcium antagonist vs. placebo
11More intensive vs. less intensive
12ACE inhibitor vs. diuretic/beta-blocker
13Calcium antagonist vs. diuretic/beta-blocker
14ACE inhibitor vs. calcium antagonist
15STROKEComparisons of active treatments and
control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
0.72 (0.64,0.81)
ACE vs. placebo
-8/-4
0.62 (0.47,0.82)
CA vs. placebo
-4/-3
0.77 (0.63,0.95)
More vs. less
0.5
1.0
2.0
Relative Risk
16STROKEComparisons of different active treatments
BP difference (mm Hg)
Favours second listed
Favours first listed
RR (95 CI)
2/0
1.09 (1.00,1.18)
ACE vs. D/BB
1/0
0.93 (0.86,1.00)
CA vs. D/BB
1/1
1.12 (1.01,1.25)
ACE vs. CA
0.5
1.0
2.0
Relative Risk
17CORONARY HEART DISEASEComparisons of active
treatments and control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
0.80 (0.73,0.88)
ACE vs. placebo
-8/-4
0.78 (0.62,0.99)
CA vs. placebo
-4/-3
More vs. less
0.95 (0.81,1.11)
0.5
1.0
2.0
Relative Risk
18CORONARY HEART DISEASEComparisons of different
active treatments
BP difference (mm Hg)
Favours first listed
Favours second listed
RR (95 CI)
2/0
ACE vs. D/BB
0.98 (0.91,1.05)
1/0
CA vs. D/BB
1.01 (0.94,1.08)
1/1
ACE vs. CA
0.96 (0.88,1.04)
0.5
1.0
2.0
Relative Risk
19HEART FAILUREComparisons of active treatments
and control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
0.82 (0.69,0.98)
ACE vs. placebo
-8/-4
1.21 (0.93,1.58)
CA vs. placebo
-4/-3
0.84 (0.59,1.18)
More vs. less
0.5
1.0
2.0
Relative Risk
20HEART FAILUREComparisons of different active
treatments
BP difference (mm Hg)
Favours first listed
Favours second listed
RR (95 CI)
2/0
ACE vs. D/BB
1.07 (0.96,1.19)
1/0
CA vs. D/BB
1.33 (1.21,1.47)
1/1
ACE vs. CA
0.82 (0.73,0.92)
0.5
1.0
2.0
Relative Risk
21MAJOR CARDIOVASCULAR EVENTSComparisons of active
treatments and control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
ACE vs. placebo
0.78 (0.73,0.83)
-8/-4
0.82 (0.71,0.95)
CA vs. placebo
-4/-3
More vs. less
0.85 (0.76,0.95)
0.5
1.0
2.0
Relative Risk
22MAJOR CARDIOVASCULAR EVENTS Comparisons of
different active treatments
BP difference (mm Hg)
Favours first listed
Favours second listed
RR (95 CI)
2/0
ACE vs. D/BB
1.02 (0.98,1.07)
1/0
CA vs. D/BB
1.04 (1.00,1.09)
ACE vs. CA
1/1
0.97 (0.92,1.03)
0.5
1.0
2.0
Relative Risk
23CARDIOVASCULAR DEATHComparisons of active
treatments and control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
ACE vs. placebo
0.80 (0.71,0.89)
-8/-4
CA vs. placebo
0.78 (0.61,1.00)
-4/-3
More vs. less
0.93 (0.77,1.11)
0.5
1.0
2.0
Relative Risk
24CARDIOVASCULAR DEATHComparisons of different
active treatments
BP difference (mm Hg)
Favours first listed
Favours second listed
RR (95 CI)
2/0
ACE vs. D/BB
1.03 (0.95,1.11)
1/0
CA vs. D/BB
1.05 (0.97,1.13)
1/1
ACE vs. CA
1.03 (0.94,1.13)
0.5
1.0
2.0
Relative Risk
25TOTAL MORTALITYComparisons of active treatments
and control
BP difference (mm Hg)
Favours active
Favours control
RR (95 CI)
-5/-2
ACE vs. placebo
0.88 (0.81,0.96)
-8/-4
CA vs. placebo
0.89 (0.75,1.05)
-4/-3
More vs. less
0.96 (0.84,1.09)
0.5
1.0
2.0
Relative Risk
26TOTAL MORTALITYComparisons of different active
treatments
BP difference (mm Hg)
Favours first listed
Favours second listed
RR (95 CI)
2/0
ACE vs. D/BB
1.00 (0.95,1.05)
1/0
CA vs. D/BB
0.99 (0.95,1.04)
1/1
ACE vs. CA
1.04 (0.98,1.10)
0.5
1.0
2.0
Relative Risk
27Angiotensin receptor blocker vs. other
28Angiotensin receptor blocker vs. other
BP difference (mm Hg)
Favours ARB
Favours other
Outcome
RR (95 CI)
-2/-1
0.79 (0.69,0.90)
Stroke
0.96 (0.85,1.09)
CHD
-2/-1
-2/-1
Heart failure
0.84 (0.72,0.97)
-2/-1
Major CV events
0.90 (0.83,0.96)
CV death
0.96 (0.85,1.08)
-2/-1
Total mortality
0.94 (0.86,1.02)
-2/-1
0.5
1.0
2.0
Relative Risk
29Role of blood pressure reduction
- Are differences in cardiovascular outcomes
between randomised groups related to observed
differences in blood pressure?
30Stroke
ACE/CA
ACE/DBB
Relative risk of stroke
ARB/other
ACE/plac
CA/DBB
More/less
CA/plac
Systolic blood pressure difference between
randomised groups (mmHg)
31Stroke
Relative risk of stroke
Systolic blood pressure difference between
randomised groups (mmHg)
32Coronary Heart Disease
1.50
1.25
Relative risk of CHD
1.00
0.75
0.50
0.25
-10
-8
-6
-4
-2
0
2
4
Systolic blood pressure difference between
randomised groups (mmHg)
33Heart Failure
1.50
Relative risk of heart failure
1.25
1.00
0.75
0.50
0.25
-10
-8
-6
-4
-2
0
2
4
Systolic blood pressure difference between
randomised groups (mmHg)
34Major Cardiovascular Events
Relative risk of major CVD
Systolic blood pressure difference between
randomised groups (mmHg)
35Cardiovascular Deaths
Relative risk of CV death
Systolic blood pressure difference between
randomised groups (mmHg)
36Total mortality
Relative risk of death
Systolic blood pressure difference between
randomised groups (mmHg)
37Conclusions I
- Similar net effects on total cardio-vascular
events of - ACE inhibitors
- Calcium antagonists
- Diuretics/beta-blockers
- ARBs also effective in reducing total
cardiovascular events
38Conclusions II
- ACE-inhibitor- and diuretic/beta-blocker-based
regimens more effective than calcium antagonists
for preventing heart failure - Calcium antagonists may be more effective for
stroke prevention - More intensive blood pressure lowering produces
larger reductions in stroke and total
cardiovascular events
39Conclusions III
- Size of blood pressure difference between
randomised groups closely associated with
reduction in risk (except for heart failure) - Size of blood pressure reduction appears to be an
important determinant of outcome
40Acknowledgements
- Collaborating Trialists L Agodoa, C Baigent, H
Black, JP Boissel, B Brenner, M Brown, C Bulpitt,
R Byington, J Chalmers, R Collins, J Cutler, B
Dahlof, B Davis, J Dens, R Estacio, R Fagard, K
Fox, L Hansson (deceased), R Holman, L Hunsicker,
J Kostis, K Kuramoto, E Lewis, L H Lindholm, J
Lubsen, S MacMahon, E Malacco, G Mancia, B Neal,
C Pepine, M Pfeffer, B Pitt, P Poole-Wilson, G
Remuzzi, P Ruggenenti, R Schrier, P Sever, P
Sleight, J Staessen, K Teo, R Turner (deceased),
P Whelton, L Wing, Y Yui, S Yusuf, A Zanchetti.
Executive Committee S MacMahon, C Baigent, J
Cutler, R Fagard, P Whelton, S Yusuf.
Coordinating Centre C Algert, J Chalmers, N
Chapman, S MacMahon, B Neal, F Turnbull, M
Woodward. Financial support Central
coordination of this project is supported by the
National Health and Medical Research Council of
Australia . Thanks also to C Anderson, D
Catellier, W Elliott, L Elvelin, A Ferraro, G
Grandits, E Handberg, L Hemphill, J Lanke, H
Merianos, B Mullane, C Palmer, V Perkovic, J
Pogue, S Pressel, D Ramjit, C Reid, A Rodgers, I
Stratton, L Thijs, J Wang, I Warnold and K
Willson.
41Blood Pressure Lowering Treatment Trialists
CollaborationSecond cycle of overview analyses