AIRE: Acute Infarction Ramipril Efficacy study

1
AIRE Acute Infarction Ramipril Efficacy study

• Purpose
• To determine whether the ACE inhibitor ramipril
  reduces mortality in patients with evidence of
  heart failure after MI
• Reference
• The Acute Infarction Ramipril Efficacy (AIRE)
  Study Investigators. Effect of ramipril on
  mortality and morbidity of survivors of acute
  myocardial infarction with clinical evidence of
  heart failure. Lancet 19933428218.

2
AIRE Acute Infarction Ramipril Efficacy study -
TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled
• Patients
• 2006 patients, aged gt18 years, with evidence of
  heart failure 310 days after MI patients with
  severe heart failure (usually NYHA class IV) or
  ongoing ischemia excluded
• Follow up and primary endpoint
• Average 15 months follow up. Primary endpoint
  all-cause mortality
• Treatment
• Placebo or ramipril initiated at 2.5 mg twice
  daily increased to 5 mg twice daily after 2
  days if tolerated

3
AIRE Acute Infarction Ramipril Efficacy study-
RESULTS -

• Significant reduction in all-cause mortality in
  ramipril group compared with placebo (17 vs. 23,
  relative risk reduction 23, P0.002)
• Reduction in mortality apparent as early as 30
  days and consistent across a wide range of
  subgroups
• Fewer patients in ramipril group developed
  severe/resistant heart failure
• No significant reduction in reinfarction or
  stroke
• Drug well tolerated, as defined by withdrawal
  rate from trial only marginally higher with
  ramipril

4
AIRE Acute Infarction Ramipril Efficacy study-
RESULTS continued-

All-cause mortality
Cumulative
35
Placebo
mortality
30
()
Ramipril
25
20
15
10
Relative hazard 0.73 (95 CI 0.60

0.89)
5
P0.002
0
0
6
12
18
24
30
Months after randomization
No. at risk
1004
Ramipril
889
592
290
123
45
982
Placebo
845
575
287
98
44
AIRE Study Investigators.
Lancet
1993
342
821

8.
5
AIRE Acute Infarction Ramipril Efficacy study-
RESULTS continued-

Effect of ramipril on subgroups
Favors
Favors
Favors
Favors
ramipril
placebo
ramipril
placebo
Age
Hypertension
lt65 years
No


gt65 years
Yes
Sex
Thrombolysis
Male
No


Female
Yes
MI to
Aspirin
lt5 days
No
randomization

gt5 days
Yes
Angina
Beta-blocker
No
No
Yes
Yes
Relative hazard
Relative hazard
0.4
0.6
0.8
1
1.4
0.4
0.6
0.8
1
1.4
1.2
1.6
1.2
1.6
AIRE Study Investigators.
Lancet
1993
342
821

8.
6
AIRE Acute Infarction Ramipril Efficacy study-
RESULTS continued-

Primary and secondary outcomes
Primary endpoint
Death






Secondary events validated by



outcomes subcommittee
Severe/resistant heart failure
Reinfarction
Stroke
AIRE Study Investigators.
Lancet
1993
342
821

8.
7
AIRE Acute Infarction Ramipril Efficacy study -
SUMMARY -

• In patients with non-severe heart failure after
  MI, ramipril commenced 310 days after MI and
  continued for a mean 15-month period
• Significantly reduced all-cause mortality
• Conferred benefit independent of age, sex,
  hypertension, angina or concomitant therapy