HOPETOO: Results of the HOPE Study Extension

1
HOPE-TOO Results of the HOPE Study Extension

2
HOPE-TOO Study objectives

• Assess whether the benefits observed during the
  HOPE trial were maintained during an additional
  2.6 years of follow-up
• Assess whether the benefits observed during the
  HOPE trial were observed in subgroups based on
  risk and ancillary treatment

3
HOPE-TOO Study design
HOPE trial extension 2.6 years
174 study centers
HOPE-TOO participants (n 4528)
Ramipril patientsfrom HOPE
Placebo patientsfrom HOPE
Open-labelACEI therapy(n 2317)
Open-label ACEI therapy(n 2211)
Follow-up ACEI therapy gt 90 ramipril
HOPE-TOO Heart Outcomes Prevention Evaluation
The Ongoing Outcomes
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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Major CV events and new diagnosis of diabetes
for combined in-trial and post-trial periods
No. of patients ()
Ramipril (n 3393)
Placebo (n 3393)
RR (95 CI)
P
MI, stroke, or CV death
699 (20.6)
820 (24.2)
0.83 (0.750.91)
0.0002
485 (14.3)
581 (17.1)
0.81 (0.720.92)
0.0007
MI
0.79 (0.650.97)
Stroke
174 (5.1)
215 (6.3)
0.023
327 (9.6)
0.86 (0.741.00)
374 (11.0)
0.045
CV death
0.84 (0.760.92)
Revascularization
880 (25.9)
0.0003
767 (22.6)
New diagnosis of diabetes
152 (7.3)
0.69 (0.560.85)
216 (10.3)
0.0006
Calculated by log-rank test and data on all
participants in the study extension, censored for
period of observation
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE-TOO Primary outcome (CV death, MI, stroke)
30
25
20
Primary outcome( HOPE-TOO patients)
15
Placebo
10
RRR 17 P 0.0002
Ramipril
5
0
4
5
6
Years
0
1
2
3
7
46524645
44324456
42044256
39814079
36473789
27192819
19232075
15501731
RRR relative risk reduction
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE-TOO Additional reduction in major CV
events and new-onset diabetes
New-onset diabetes
Revascularization
MI
0
5
10
15
Reduction
16
20
19
25
30
35
34
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-41.
7
HOPE-TOO Additional reduction in MI
25
MI( HOPE-TOO patients)
Placebo
RRR 19P 0.0007
Ramipril
0
Years
46524645
44744484
42824309
40884159
37703875
28142900
19992137
16121791
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
8
HOPE-TOO Additional reduction in new-onset
diabetes
12
10
8
New-onsetdiabetes( HOPE-TOO patients)
6
Placebo
4
RRR 31 P 0.0006
2
Ramipril
0
5
1
2
3
4
6
7
Years
28832837
28032763
10211092
27042672
26002587
23922431
18131853
12691324
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE-TOO Sustained reductionin CV death
15
CV death( HOPE-TOO patients)
Placebo
RRR 14P 0.045
Ramipril
0
Years
46524645
45694567
18081946
44534448
43094346
40274097
30613100
22032295
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
10
HOPE-TOO Sustained reductionin stroke
10
Stroke( HOPE-TOO patients)
Placebo
RRR 21P 0.023
Ramipril
0
Years
46524645
45234539
43674391
41884263
38874000
29533011
21152225
17341876
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE/HOPE-TOO Benefits at all levelsof risk and
with other life-saving drugs
Primary outcome CV death/MI/stroke
HOPE
HOPE-TOO
Group
No. of patients
Placebo rate
Interaction P-value
Group
No. of patients
Placebo rate
Interaction P-value
Overall
9297
17.7
Overall
6786
24.2
Low
3083
9.8
Low
2299
15.2
0.51
0.67
Medium
3100
16.1
Medium
2247
22.6
High
3114
26.9
High
2240
34.5
0.0019
0.0043
ASA
6813
17.3
ASA
4974
23.5
ASA
2484
19.1
ASA
1812
26.0
0.89
0.20
3673
18.2
2712
26.2
BB
BB
BB
5624
17.4
BB
4074
22.8
0.68
0.78
Lipid meds
2658
14.0
Lipid meds
1960
18.7
Lipid meds
6639
19.3
Lipid meds
4826
26.4
0.6
0.8
1.0
1.2
0.6
0.8
1.0
1.2
RR (95 CI)
RR (95 CI)
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
12
HOPE/HOPE-TOO Benefits at all levelsof risk and
with other life-saving drugs
New-onset diabetes
HOPE
HOPE-TOO
Group
No. of patients
Placebo rate
Interaction P-value
Group
No. of patients
Placebo rate
Interaction P-value
Overall
5720
5.4
Overall
4183
10.3
Low
2079
5.9
Low
1556
11.3
0.87
0.55
Medium
2091
4.2
Medium
1516
8.4
High
1550
6.3
High
1111
11.6
0.037
0.44
ASA
4833
5.5
ASA
3539
10.4
ASA
887
4.8
ASA
644
9.5
0.15
0.23
2658
4.9
1966
10.0
BB
BB
BB
3062
5.8
BB
2217
10.6
0.12
0.97
Lipid meds
1859
6.6
Lipid meds
1368
12.4
Lipid meds
3861
4.8
Lipid meds
2815
9.2
RR (95 CI)
RR (95 CI)
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE-TOO Study conclusions
The benefits of ramipril were maintained during
post-trial follow-up for CV death, stroke, and
hospitalization for heart failure Additional
reductions in MI, revascularization and new-onset
diabetes were also observed despite similar rates
of ACEI use in the randomized groups The
reduction in CV outcomes demonstrated in the HOPE
trial is most likely an underestimate of the full
effects of long-term ramipril therapy Subgroup
analyses demonstrate the benefits observed are
additive to those of other life-saving therapies,
and extend to all patients with vascular disease,
independent of their baseline risk
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
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HOPE-TOO Implications for clinical practice
Results support earlier vs later initiation of
ACEI therapy Benefit demonstrated across a
3-fold range in baseline risk (event rate 1.9
6 per yr) Benefits are additive to other
proven therapies (ASA, ?-blockers,
lipid-lowering agents)
ACE inhibition therapy should be used in most
patients with vascular disease or diabetes and
additional risk factors
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.