A randomized prospective trial of intravenous nitroglycerin in patients with acute myocardial infarction.

Abstract

A prospective randomized study of i.v. nitroglycerin (TNG) administered for 48 h after acute infarction was undertaken to determine whether clinical improvement and/or evidence of preservation of ischemic myocardium could be demonstrated. Patients (104) were randomly assigned to TNG (n = 56) and placebo groups (n = 48). TNG was infused at a rate sufficient to lower mean arterial pressure 10%, monitored noninvasively. When all TNG- and placebo-treated patients were compared, no significant differences in clinical or laboratory outcomes could be demonstrated. TNG- and placebo-treated patients were retrospectively subdivided into early and late treatment groups (treatment begun < 10 h vs. .gtoreq. 10 h after onset of symptoms). Early TNG treatment was associated with a lower incidence of infarct complications within the first 10 days, defined by new congestive heart failure, infarct extension or cardiac death (15% in early TNG compared with a mean of 39% in the other 3 subgroups; P = 0.003). Mortality at 3 mo. was lower in the group treated early with TNG (15%) compared with a mean of 25% in the other 3 subgroups (P = NS). No significant differences were found in peak creatine kinase (CK) blood levels, creatine kinase infarct size, or preservation of precordial R waves by serial ECG mapping. Among 49 patients with pretreatment and day 7 to 14 posttreatment left ventricular ejection fraction measurements, improvement of .gtoreq. 10% occurred in 35% of TNG patients treated early compared with 6% of those treated late with TNG, 11% of those treated early with placebo and 0% of those treated late with placebo (P = 0.004). Similarly, in 68 patients in whom paired Tl scintigrams were taken, a decrease of .gtoreq. 75% in the computer-determined Tl defect score was seen in 48% of TNG patients treated early, compared with 14% of TNG patients treated late, 33% of placebo patients treated early and 0% of placebo patients treated late (P = 0.039). Patients demonstrating significant scintigraphic improvement were treated earlier, tended to have less severe initial scintigraphic abnormalities, inferior rather than anterior infarctions, a longer history of angina and no prior history of heart failure. Thus i.v. TNG could not be shown to result in significant improvement in clinical or scintigraphic outcomes when the patient population was analyzed as a whole. After retrospective subgroup analysis, i.v. TNG could be shown to protect ischemic myocardium in the subset of patients with small-to-moderate sized myocardial infarctions when treatment was begun within 10 h of the onset of symptoms. Apparently, future clinical trials designed to show a reduction in infarct size might limit patient entry to those admitted early after symptom onset and those with significant abnormalities in their admission scintigraphic studies. Larger-scale studies are needed to determine whether TNG therapy can significantly reduce mortality and to further define the population of patients who may profit most from this treatment.