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 enzyme (ACE) inhibitor captopril in survivors of myocardial infarction with left ventricular dysfunction would prevent a further deterioration of ventricular function and thereby improve clinical outcome. The study did demonstrate that randomization to the ACE inhibitor resulted in improved survival and, specifically, lessened cardiovascular deaths. The prestudy rationale that less ventricular enlargement would be observed in ACE inhibitor treated patients was validated by an echocardiographic substudy. As anticipated, fewer patients treated with the ACE inhibitor went on to manifest the prespecified definitions of more overt congestive heart failure. Importantly, not only were the manifestations of congestive heart failure reduced, there were fewer fatal events subsequent to development of failure. Although this concept of attenuation of progressive remodeling leading to benefits was upheld, the study also yielded other observations to support the generation of new hypotheses to explain a component of the overall benefit of ACE inhibitor therapy. Particularly attractive, and supported by observations from the Studies of Left Ventricular Dysfunction (SOLVD) studies, is the reduction in myocardial infarction and subsequent death following myocardial infarction with chronic ACE inhibitor therapy. These clinical observations point to an important potentially modifiable interface between the renin-angiotensin system and the risk of experiencing a coronary atherosclerotic event. Although the value of ACE inhibition therapy in patients with acute and chronic myocardial infarction is already clinically apparent, new mechanistic hypotheses generating information have provided further stimulus for basic and clinical research which will undoubtedly lead to an even greater understanding of the pathophysiology of myocardial infarction. Am J Hypertens 1994;7:106S-111S