Long-Term Results from the SAVE Trial
ABSTRACT & COMMENTARY
Synopsis: Left ventricular dilatation is progressive and associated with reduced performance that is unaffected by captopril therapy after one year.
Source: St. John Sutton M, et al. Circulation 1997; 96:3294-3299.
The survival and ventricular enlargement (SAVE) study of patients after acute MI who were randomized to placebo or captopril therapy showed that there was less mortality and reduced left ventricular (LV) dilatation after one year of therapy with captopril. St. John Sutton and colleagues analyzed the SAVE subpopulation with echocardiography for two years to further evaluate the LV dilatation phenomenon after one year. The echo substudy consisted of 512 patients post-acute MI who had LV ejection fraction (EF) less than 40% and were treated with a study drug for a minimum of two years (average, 3.5 yrs). Of these, 373 had baseline one- and two-year echocardiograms and are the basis of this study. LV diastolic cavity area increased progressively from 70 cm2 at baseline to 72 cm2 at one year and 73 cm2 at two yearsas did systolic cavity area (50 to 52 to 54 cm2). Although captopril attenuated LV dilatation (P < 0.05), the effect after one year was proportional to the first year effect, and dilatation in the second year was parallel in the two treatment groups. LV dilatation was associated with LV distortion, and the LV became more spherical. LV dilatation was accompanied by deterioration in LV performance. More than one-third of the patients met predetermined criteria for abnormal LV dilatation, and more of these patients experienced more than a 0.09 unit fall in EF (25%), compared to those with normal sized LVs (7%; P < 0.001). Echo estimates of LV dilatation and shape predicted cardiovascular death (RR, 0.82; CI, 0.75-0.92; P < 0.001) and development of heart failure (RR, 0.87; CI, 0.71-0.93; P = 0.002) but not recurrent MI. The authors conclude that cardiovascular death or LV dilatation occurred in 50% of post-MI patients with initial EF less than 40% by two years, and that LV dilatation is progressive and associated with reduced performance that is unaffected by captopril therapy after one year.
COMMENT BY MICHAEL H. CRAWFORD, MD
This extensive analysis of the long-term SAVE study and the echocardiographic substudy challenges traditional thinking about the time course of healing post-MI. Pathologic studies have suggested that MI healing is complete in a few months, but this living study shows continued insidious dilatation and deterioration of function for two years in more than one-third of acute MI patients with baseline EFs less than 40%. Also, this study shows that ACE inhibitor therapy appears to be ineffective in preventing this progressive remodeling after one year. Furthermore, these findings probably underestimate the magnitude of the problem since they reflect data on the two-year survivorsignoring the higher risk patients who died during the two years.
Progressive LV dilatation was not inevitable in these post-MI patients with low EF, but what protected two-thirds of the patients from achieving abnormal LV dilatation is not known. ACE inhibitor therapy obviously played a role during the first year. The presence of an open infarct artery may have been important, but there are no data on this feature in SAVE. Of note, many patients had revascularization after randomization or sustained another MI, both of which could influence the results of this study. At present, we do not know how to keep our patients in the favorable group and whether we need to continue ACE inhibitors after one year.
Long-term follow-up in the SAVE trial shows that:
a. captopril has reduced effectiveness after one year.
b. LV remodeling is complete by six months.
c. LVEF gradually improves between years one and two.
d. LV remodeling is strongly correlated with recurrent MI.
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