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 1993;342:821–8.

2. AIRE: Acute Infarction Ramipril Efficacy study - TRIAL DESIGN - Design Multicenter, multinational, randomized, double-blind, placebo- controlled Patients 2006 patients, aged >18 years, with evidence of heart failure 3–10 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%, P=0.002) 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- Months after randomization 0 0 1004 982 Ramipril Placebo No. at risk 889 845 592 575 290 287 123 98 45 44 612182430 15 10 5 35 30 25 20 All-cause mortality Placebo Ramipril Cumulative mortality (%) Relative hazard 0.73 (95% CI 0.60–0.89) P=0.002 AIRE Study Investigators.Lancet 1993;342:821–8.

5. AIRE: Acute Infarction Ramipril Efficacy study - RESULTS continued- 0.40.6 Relative hazard 0.81 1.2 Effect of ramipril on subgroups <65 years >65 years Male Female <5 days >5 days No Yes Favors ramipril Favors placebo Favors ramipril Favors placebo AIRE Study Investigators.Lancet 1993;342:821–8. Age: Sex: MI to randomization: Angina: 1.4 1.6 0.40.60.81 1.2 No Yes No Yes No Yes No Yes Hypertension: Thrombolysis: Aspirin: Beta-blocker: 1.4 1.6

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. Ramipril (n=1004) No. (%) 170 (17) 143 (14) 81 (8) 25 (2) Placebo (n=982) No. (%) 222 (23) 178 (18) 88 (9) 17 (2)

7. AIRE: Acute Infarction Ramipril Efficacy study - SUMMARY - In patients with non-severe heart failure after MI, ramipril commenced 3–10 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