MECHANISTIC LESSONS FROM THE SAVE STUDY

The Survival and Ventricular Enlargement (SAVE) study was designed to test the hypothesis that chronic use of the angiotensin-converting enz yme (ACE) inhibitor captopril in survivors of myocardial infarction wi th left ventricular dysfunction would prevent a further deterioration of ventricular function and thereby improve clinical outcome. The stud y did demonstrate that randomization to the ACE inhibitor resulted in improved survival and, specifically, lessened cardiovascular deaths. T he prestudy rationale that less ventricular enlargement would be obser ved in ACE inhibitor treated patients was validated by an echocardiogr aphic substudy. As anticipated, fewer patients treated with the ACE in hibitor went on to manifest the prespecified definitions of more overt congestive heart failure. Importantly, not only were the manifestatio ns of congestive heart failure reduced, there were fewer fatal events subsequent to development of failure. Although this concept of attenua tion of progressive remodeling leading to benefits was upheld, the stu dy also yielded other observations to support the generation of new hy potheses to explain a component of the overall benefit of ACE inhibito r therapy. Particularly attractive, and supported by observations from the Studies of Left Ventricular Dysfunction (SOLVD) studies, is the r eduction in myocardial infarction and subsequent death following myoca rdial infarction with chronic ACE inhibitor therapy. These clinical ob servations point to an important potentially modifiable interface betw een the renin-angiotensin system and the risk of experiencing a corona ry atherosclerotic event. Although the value of ACE inhibition therapy in patients with acute and chronic myocardial infarction is already c linically apparent, new mechanistic hypotheses generating information have provided further stimulus for basic and clinical research which w ill undoubtedly lead to an even greater understanding of the pathophys iology of myocardial infarction.