HOPE: Heart Outcomes Prevention Evaluation study

1
HOPE Heart Outcomes Prevention Evaluation study

• Purpose
• To evaluate whether the long-acting ACE
  inhibitor ramipril and/or vitamin E reduce the
  incidence of cardiovascular morbidity and
  mortality in a high-risk population
• References
• The HOPE Study Investigators. Effects of an
  angiotensin-converting-enzyme inhibitor,
  ramipril, on cardiovascular events in high-risk
  patients. N Engl J Med 200034214553.
• The HOPE Study Investigators. Vitamin E
  supplementation and cardiovascular events in
  high-risk patients. N Engl J Med 200034215460.

2
HOPE Heart Outcomes Prevention Evaluation
study- TRIAL DESIGN -

• Treatment
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled parallel-group,
  two-by-two factorial study
• Patients
• 55 years or older with history of vascular
  disease or diabetes mellitus, plus one other
  cardiovascular risk factor patients with stroke
  or MI in previous month, heart failure or
  evidence of low ejection fraction excluded
• Follow up and primary endpoint
• Mean 5.0 years follow up for ramipril (4.5 for
  vitamin E). Primary endpoint composite of MI,
  stroke or cardiovascular death

3
HOPE Heart Outcomes Prevention Evaluation
study- TRIAL DESIGN continued -

• Pre-randomization therapy
• Ramipril 2.5 mg once daily (710 days), then
  placebo (1014 days). Patients with side effects,
  abnormal serum creatinine/potassium, or
  noncompliance subsequently excluded
• Treatment
• 9297 patients (2480 women, 6817 men) randomly
  assigned to receive one of four treatments for 5
  years
• Ramipril 2.5 mg for 1 week, 5 mg for 3 weeks,
  then 10 mg vitamin E 400 IU daily
• Ramipril 2.5 mg for 1 week, 5 mg for 3 weeks,
  then 10 mg placebo matching vitamin E treatment
• Placebo matching ramipril treatment vitamin E
  400 IU daily
• Placebo matching ramipril treatment placebo
  matching vitamin E treatment

4
HOPE Heart Outcomes Prevention Evaluation
study- RESULTS -

• Ramipril vs. placebo
• Study halted 6 months early on recommendation of
  monitoring board because of consistent benefit of
  ramipril
• Composite primary endpoint of MI, stroke or death
  from cardiovascular causes significantly lower in
  ramipril group (14.0 vs. 17.8, relative risk
  0.78, Plt0.001)
• Individual primary endpoints (MI, stroke, death
  from cardiovascular causes), all-cause mortality,
  and secondary outcomes of revascularization and
  complications related to diabetes, significantly
  lower in ramipril group
• New diagnosis of diabetes significantly lower in
  ramipril group (3.6 vs. 5.4, relative risk 0.66,
  Plt0.001)
• Drug well tolerated as defined by permanent
  discontinuation of treatment (28.9 of ramipril
  group versus 27.3 placebo)

5
HOPE Heart Outcomes Prevention Evaluation
study- RESULTS continued -

• Vitamin E vs. placebo
• No benefit shown for vitamin E vs. placebo
• No significant difference in composite primary
  endpoint of MI, stroke or cardiovascular death in
  ramipril group (16.0 vs. 15.5, relative risk
  1.05, P0.33)
• No significant difference in individual primary
  endpoints or secondary cardiovascular outcomes or
  death from any cause
• No significant adverse effects of vitamin E

6
HOPE Heart Outcomes Prevention Evaluation
study- RESULTS continued -

MI, stroke or death from cardiovascular causes
Proportion
0.20
of patients
0.15
0.10
0.05
Placebo
P lt0.001
Ramipril
0.00
0
500
1000
1500
Days of follow up
The Hope Study Investigators.
N Engl J Med
2000
342
145

53.
7
HOPE Heart Outcomes Prevention Evaluation
study- RESULTS continued -

Primary outcome and deaths from any cause
Relative risk
P
(95 CI)
MI, stroke, or death from
0.78 (0.70

0.86)
lt0.001
cardiovascular causes
0.74 (0.64

0.87)
lt0.001
Death from cardiovascular causes
0.80 (0.70

0.90)
lt0.001
MI
0.68 (0.56

0.84)
lt0.001
Stroke
1.03 (0.85

1.26)
0.74
Death from noncardiovascular causes
0.84 (0.75

0.95)
0.005
Death from any cause
The Hope Study Investigators.
N Engl J Med
2000
342
145

53.
8
HOPE Heart Outcomes Prevention Evaluation
study- RESULTS continued -

Secondary outcomes and new diagnosis of diabetes
Relative
P
risk
Secondary outcomes
Revascularization
0.85 (0.770.94)
0.002
Hospitalization for unstable angina
0.98 (0.871.10)
0.68
Complications related to diabetes
0.84 (0.720.98)
0.03
Hospitalization for heart failure
0.88 (0.701.10)
0.25
New diagnosis of diabetes
0.66 (0.510.85)
lt0.001
The Hope Study Investigators.
N Engl J Med
2000
342
145

53.
9
HOPE Heart Outcomes Prevention Evaluation study
- SUMMARY -

• In high-risk patients not known to have low
  ejection fraction or heart failure
• Ramipril
• Reduced rates of death, MI, stroke and
  revascularization
• Reduced rates of new diagnosis of diabetes and
  complications due to diabetes
• Vitamin E
• Had no effect on outcomes