EFFECT OF RAMIPRIL ON MORBIDITY AND MODE OF DEATH AMONG SURVIVORS OF ACUTE MYOCARDIAL-INFARCTION WITH CLINICAL-EVIDENCE OF HEART-FAILURE - A REPORT FROM THE AIRE STUDY INVESTIGATORS

Background The importance of the effects of ACE inhibitors on sudden d eath, progressive heart failure and recurrent infarction to the reduct ion in overall mortality in heart failure and after myocardial infarct ion is disputed. Methods The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipril 5 mg b.d. or matching plac ebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Results Fewer patients deve loped severe resistant heart failure as their first validated end-poin t on ramipril, despite the greater number of at-risk survivors, compar ed to placebo (n=143 vs 178; risk reduction 23%; CI5 to 39%; P=0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespecti ve of treatment allocation 182 (46%) patients developed resistant hear t failure prior to death. A validated acute or remote myocardial reinf arction occurred in 76 (19%) patients prior to death and chest pain oc curred in 90 (23%) patients around the time of death suggesting an isc haemic element to these deaths. Eighty deaths occurred on the index ad mission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ra mipril reduced the risk of sudden death by 30% (95% CI; 8-47%; P=0.011 ). However, overall, 45% of those patients who died suddenly had sever e or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. 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 w ere not significantly different. However, 38% of the reduction in over all mortality was from the subgroup with sudden death who had develope d prior severe resistant heart failure (placebo n=35, ramipril n=15), again emphasizing the marked benefit in preventing failure. Ramipril d id not selectively alter the proportion of in- to out-of-hospital deat hs. Conclusion Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early aft er myocardial infarction. Retarding the progression of heart failure a ppears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.