Principal Findings:

All cause mortality significantly lower for Ramipril (17%) than placebo (23%).

Risk reduction with Ramipril was 27% (95% CI, 11% to 40%; p = 0.002).

Mortality reduction apparent as early as 30 days after initiation of treatment.

Risk reduction for first secondary endpoint was 19% (.95 CI 5-31%; p = 0.008).

Mortality benefit consistent across a range of subgroups with a trend toward less benefit in patients < 65 years and those not requiring a diuretic.

Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure.

At an average follow-up time of 15 months after randomization, all-cause mortality was lower in the ramipril group (16.9%) compared to placebo (22.6%), equivalent to an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Three years after the AIRE study closed, mortality status of all patients was assessed through government records. Follow-up was for a minimum of 42 months and a mean of 59 months. Death from all causes had occurred in 83 (27.5%) of 302 patients randomly assigned ramipril and (38.9%) of 301 patients randomly assigned placebo. This 11.4% absolute mortality reduction was equal to a relative risk reduction of 36% (95% CI 15-52%; p = 0.002).