Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes
mellitus: results of the HOPE study and MICRO-HOPE substudy
HOPE Study Investigators. Lancet 2000;355:253-9 (January 22)
Study Type: POEM
Purpose: In diabetics, does ramipril prevent nephropathy, lower death from cardiovascular causes, MI, or stroke?
Study Duration: 4.5 years, n = 3,654
Patients: ~66 years old, BP = ~140/80, ~65:35 male:female, ~80% had some history of coronary artery disease, 10% had a stroke or TIA, ~45% had
PVD, ~38% had diabetes, ~65% elevated cholesterol, ~14% smoke, ~20% with microalbuminuria, ~8% with LVD, most patients were on some
regimen of drug therapy (i.e., 75% on asa, 28% of lipid, 15% on diuretics, ~40% on beta-blockers, ~46% on CCB)
~50% were on oral agents alone vs ~25% insulin alone, 18% diet alone, 5% on combination
Trial Design: multicenter (127), double-blinded, randomized, ramipril 10 mg +/- vitamin E 400 IU qd vs placebo
Inclusion: male and female, at least 55 yrs, history of coronary artery disease, stroke, PVD, diabetes + at least one of hypertension, elevated total
cholesterol, low HDL, smoking, microalbuminuria
Exclusion: heart failure, EF < 40, taking an ACEI or vit A, uncontrolled hypertension, nephropathy, MI or stroke within 4 weeks,
secondary HTN, SCr > 150 mmol/L (~1.6 mg/dL), any disorder requiring treatment with a beta-blocker, MICRO-HOPE - dipstick + proteinuria,
established diabetic nephropathy, severe renal disease, hyperkalemia
Primary Outcome Events: MI, stroke, or death from cardiovascular causes
Secondary endpoints: all-cause-death, need for revascularization, hospitalization, diabetic complications
MICRO-HOPE endpoints - prevention of microalbuminuria, or nephropathy in participating diabetics, various labs were drawn
1.
*
*
*
*
*
*
Are the results valid?
randomized? yes
double-blinded? yes
placebo-controlled? yes
placebo run in ? yes
patient accountability? yes
were groups similar? yes
2.
What were the results?
Primary endpoints
MI, stroke, or death from CV
Death from CV causes
MI
Stroke
Death from all-cause
Secondary endpoints
Revascularization
Unstable angina
Heart failure
Nephropathy
TIA’s
Laser therapy
Dialysis
Laser+nephropathy+dialysis
3.
*
*
*
*
*
Ramipril
Placebo
ARR
NNT
P
15.3%
6.2%
10.2%
4.2%
10.8%
19.8%
9.7%
12.9%
6.1%
14%
4.5
3.5
2.7
1.9
3.2
22
29
37
53
31
.0004
.0001
.01
.0074
.0001
14%
16.4%
2.4
42
6.5%
4.4%
8.4%
5.9%
1.9
1.5
53
67
15.1%
17.6%
2.5
40
.031
NS
NS
.027
.04
NS
NS
.036
Will the results help me?
66% were still on the drug at 5 years
cough caused more study discontinuance (NNH = 20)
HbA1c was similar in both groups at the end of the study
BP reduction was greater in the ramipril group, but small compared to other studies, yet the same cardiovascular risk reduction
For every 1000 diabetics treated with ramipril, we would expect to prevent 45 MI, strokes or cardiovascular deaths,
24 revascularization surgeries, 18 cases of nephropathy, and 15 TIA’s, also 25 patients would be prevented of laser surgery,
nephropathy and dialysis (combined endpoints).
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