vbwg hope-too: results of the hope study extension
TRANSCRIPT
VBWG
HOPE-TOO: Rationale
• HOPE-TOO was an extension of the HOPE trial, which examined the effects of ACE inhibition in reducing major CV events in high-risk patients with vascular disease or diabetes
• HOPE-TOO was designed to assess whether the CV and metabolic benefits of ramipril were sustained over time and occurred in subgroups based on varying risk and concomitant treatment
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
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HOPE-TOO: Study design
• 4528 HOPE patients at 174 centers who agreed to further follow-up
• Blinded treatment ended and patients were advised to use ACEI
• 2.6-year post-trial extension
• ACEI use during extension– HOPE ramipril arm (n = 2317): 72% – HOPE placebo arm (n = 2211): 68% – >90% of all HOPE-TOO patients used ramipril
Heart Outcomes Prevention Evaluation–The Ongoing Outcomes
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
VBWGMajor CV events and new diagnosis of diabetes for combined in-trial and post-trial periods
No. of patients (%)
New diagnosis of diabetes
Revascularization
Stroke
CV death
MI
MI, stroke, or CV death
Ramipril(n = 3393)
Placebo(n = 3393)
699 (20.6)
485 (14.3)
174 (5.1)
327 (9.6)
767 (22.6)
152 (7.3)
820 (24.2)
581 (17.1)
215 (6.3)
374 (11.0)
880 (25.9)
216 (10.3)
RR (95% CI) P*
0.83 (0.75–0.91)
0.81 (0.72–0.92)
0.79 (0.65–0.97)
0.86 (0.74–1.00)
0.84 (0.76–0.92)
0.69 (0.56–0.85)
0.0002
0.0007
0.023
0.045
0.0003
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. 2005;112:1339-46.
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HOPE-TOO: Primary outcome (CV death, MI, stroke)
RRR = relative risk reduction HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
30
RRR = 17%P = 0.0002
0 1 2 3 4 5 6 70
Placebo
Ramipril
Years
Primary outcome
(% HOPE-TOO patients)
25
20
15
10
5
46524645
44324456
42044256
39814079
36473789
27192819
19232075
15501731
PlaceboRamipril
n
HOPE-TOO begins
Main HOPE study ends
VBWGHOPE-TOO: Effect of ACEI on major CV events and new-onset diabetes
No. of HOPE patients (%)
New diagnosis of diabetes
Revascularization
Stroke
CV death
MI
MI, stroke,or CV death
1.31.21.11.00.90.80.70.60.50.40.3 1.4 1.5
Ramipril(n = 2317)
Placebo(n = 2211)
RR (95% CI)
220 (7.9)
146 (5.1)
59 (2.0)
133 (4.4)
235 (9.1)
48 (2.7)
225 (8.4)
169 (6.1)
56 (1.9)
126 (4.2)
259 (10.5)
70 (4.0)
*Event rates were calculated as proportions of events in those study participants who were event-free at the end of the in-trial period.
Event*
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
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HOPE-TOO: Additional reduction in MI
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
25
RRR = 19%P = 0.0007
00 1 2 3 4 5 6 7
Placebo
Ramipril
MI(% HOPE-TOO
patients)
20
15
10
5
Years46524645
44744484
42824309
40884159
37703875
28142900
19992137
16121791
PlaceboRamipril
n
HOPE-TOO begins
Main HOPE study ends
VBWGHOPE-TOO: Additional reduction in new-onset diabetes
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
12
6
2
4
0
1 2 3 4
8
10
5 6 7
Placebo
Ramipril
Years
RRR 31% P = 0.0006
HOPE-TOO begins
Main HOPE study ends
28832837
28032763
27042672
26002587
23922431
18131853
12691324
10211092
New-onsetdiabetes
(% HOPE-TOO patients)
PlaceboRamipril
n
VBWGHOPE-TOO: Sustained reduction in stroke
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
10
RRR = 21%P = 0.023
0
Placebo
Ramipril
8
6
4
2
Years46524645
45234539
43674391
41884263
38874000
29533011
21152225
17341876
0 1 2 3 4 5 6 7PlaceboRamipril
n
Stroke(% HOPE-TOO
patients)
HOPE-TOO begins
Main HOPE study ends
VBWG
HOPE-TOO: Sustained reduction in CV death
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
15
RRR = 14%P = 0.045
0
Placebo
Ramipril
10
5
Years46524645
45694567
44534448
43094346
40274097
30613100
22032295
18081946
0 1 2 3 4 5 6 7PlaceboRamipril
n
CV death(% HOPE-TOO
patients)
HOPE-TOO begins
Main HOPE study ends
VBWG
HOPE/HOPE-TOO: Benefits at all levelsof risk and with other life-saving drugs
Group No. ofpatients
Lipid meds –Lipid meds +
BB –BB +
ASA –
ASA +
High
Medium
Low
Overall 9297
3083
3100
3114
6813
2484
36735624
26586639
Placeborate
17.7
9.8
16.1
26.9
17.3
19.1
18.217.4
14.019.3
InteractionP-value
0.51
0.0019
0.89
0.68
0.6 0.8 1.0 1.2
Lipid meds –Lipid meds +
Group No. ofpatients
BB –BB +
ASA –
ASA +
High
Medium
Low
Overall 6786
2299
2247
2240
4974
1812
27124074
19604826
Placeborate
24.2
15.2
22.6
34.5
23.5
26.0
26.222.8
18.726.4
InteractionP-value
0.67
0.0043
0.20
0.78
0.6 0.8 1.0 1.2
HOPE HOPE-TOO
Primary outcome = CV death/MI/stroke
RR (95% CI) RR (95% CI)
HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
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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. 2005;112:1339-46.