Extension studies show sustained benefits with ACEI

1
Extension studies show sustained benefits with
ACEI
VBWG
AIREX CONSENSUS X-SOLVD HOPE-TOO
1997 1999 2003 2005
Treatment Ramipril Enalapril Enalapril Ramipri
l Follow-up 15 mos 10 yrs 12 yrs 7.2
yrs Characteristic Clinical HF, NYHA class
IV HF, LV High CV risk, post-MI HF dysfunct
ion no LV dysfunction no HF Results
RRR 36 Overall survival Extended Reduced
major in mortality prolonged survival CV
events and by 50 by 9.4 mo new diabetes
by 34 Summary Continue ACEI Beneficial
effect Sustained Sustained indefinitely
post-MI maintained improvement benefit
with several yrs in survival long-term
use
Dosageimportant
Hall AS et al. Lancet. 19973491493-7. Swedberg
K et al. Eur Heart J. 199920136-9. Jong P et
al. Lancet. 20033611843-8.HOPE/HOPE-TOO Study
Investigators. Circulation. 20051121339-46.
2
HOPE-TOO Study disposition
VBWG
Inclusion criteriaAge 55 years Hx CAD,
stroke, PVD ordiabetes 1 CV risk factor
Exclusion criteriaCHF, known EF lt0.4,
Uncontrolled HTN MI or stroke 4 wks current
ACEI, vit E use
174 study centers(n 6786)
Primary analysis
Placebo (n 3393)
Ramipril(n 3393)
HOPE-TOO participantsagreed to passive
follow-up(n 4528)
Early ACEI Ramipril patientsfrom HOPE
Late ACEI Placebo patients from HOPE
Open-labelACEI therapy(n 2317)
Open-labelACEI therapy(n 2211)
Follow-up ACEI therapygt90 ramipril
Adapted from HOPE/HOPE-TOO Study Investigators.
Circulation. 20051121339-46.
3
HOPE-TOO Baseline characteristics in extended
follow-up
VBWG
Ramipril ()(n 3393)
Placebo ()(n 3393)
Characteristic
CAD 79.5 81.2 MI 52.3 53.5 Stroke
11.1 11.3 PAD 40.4 43.2 Hypertension
47.1 45.0 Diabetes 38.5 38.2 Elevated total-C
64.8 66.2 Current cigarette smoking
13.4 14.2 Medications ?-Blockers
39.8 40.1 Aspirin or other antiplatelet agents
74.8 77.0 Lipid-lowering drugs
28.5 29.3 Diuretics 15.6 15.2 Calcium channel
blockers 46.1 47.3 LV hypertrophy on ECG
7.7 8.3 Microalbuminuria 19.3 20.3
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
4
HOPE-TOO Primary outcome (CV death, MI, stroke)
VBWG
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
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.
5
HOPE-TOO Additional risk reduction in major CV
events and new-onset diabetes
VBWG
New-onset diabetes
Revascularization
MI
0
5
10
Reductionwith ramipril
15
16
20
19
25
30
35
34
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-41.
6
Benefit of treatment with ACEI
VBWG
Sustained, irreversible, favorable
ventricular/vascular remodeling RAAS
blockade provides sustainable, favorable effect
on glucose homeostasis Benefits are additive
to ancillary therapy and extend to all
patients, independent of baseline risk
Earlier rather than later initiation provides
longer-term protection
HOPE/HOPE-TOO Study Investigators. Circulation.
20051121339-46.