ELECTROCARDIOGRAPHIC SUBSET ANALYSIS OF DILTIAZEM ADMINISTRATION ON LONG-TERM OUTCOME AFTER ACUTE MYOCARDIAL-INFARCTION

The effect of diltiazem on long-term outcome after acute myocardial infarction (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post-Infarction Trial and subsequently followed for 25 +/- 8 months. The study population included 855 patients (36%) with at least 1 prior AMI before the index infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a first anterior Q-wave AMI. This post hoc analysis revealed that, among patients with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac events during follow-up in the diltiazem than in the placebo group, and that the reverse was true for patients with first anterior Q-wave AMI or prior infarction. The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial primary end point (cardiac death or nonfatal reinfarction, whichever occurred first) was: first non-Q-wave AMI - 0.48 (0.26, 0.89); first inferior Q-wave AMI-0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI-1.11 (0.85, 1.44). Use of cardiac death alone as an end point gave an even more sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21); first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28 (0.68, 2.40); prior infarction-1.26 (0.90, 1.77). Further analysis revealed that these differences in the effect of diltiazem in large part reflected the different status of the 4 electrocardiographically defined subsets in terms of left ventricular function. Mean (+/- standard deviation) ejection fraction for patients with first non-Q-wave AMI (placebo, 0.53 +/- 0.13; diltiazem, 0.54 +/- 0.12) was comparable to that of patients with a first inferior Q-wave AMI (placebo, 0.52 +/- 0.10; diltiazem, 0.52 +/- 0.11), and both these first AMI subsets had a lower frequency of radiographic pulmonary congestion range (10 to 16%) during the acute infarction than did patients with first anterior Q-wave or prior AMI. Mean ejection fraction for the subset of patients with first anterior Q-wave AMI (placebo, 0.38 +/- 0.13; diltiazem, 0.40 +/- 0.12) was comparable to that of patients with at least 1 prior AMI (placebo, 0.44 +/- 0.15; diltiazem, 0.43 +/- 0.14) and the frequency of pulmonary congestion in these 2 infarct subsets ranged from 24 to 26%. The differential effect of diltiazem on postinfarction outcome in these electrocardiographically categorized AMI subsets appears closely linked to the bidirectional effect of diltiazem (beneficial in the majority of patients with well-preserved left ventricular function, harmful in the minority with impaired left ventricular function) that was elucidated in the primary Multicenter Diltiazem Post-Infarction Trial analysis. In patients with multiple infarctions complicated by left ventricular dysfunction, diltiazem appears to be detrimental. Patients with first non-Q-wave or first inferior Q-wave infarction generally have well-preserved left ventricular function and appear to benefit from diltiazem.