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

Abstract

A prospective randomized study of intravenous nitroglycerin (TNG) administered for 48 hr after acute infarction was undertaken to determine whether clinical improvement and/or evidence of preservation of ischemic myocardium could be demonstrated. One hundred four patients 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 hr vs 3 10 hr 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 three subgroups; p = .003). Mortality at 3 months was lower in the group treated early with TNG (15%) compared with a mean of 25% in the other three 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 electrocardiographic mapping. Among 49 patients with pretreatment and day 7 to 14 posttreatment left ventricular ejection fraction measurements, improvement of 3 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 = .004). Similarly, in 68 patients in whom paired thallium scintigrams were taken, a decrease of B75% in the computer-determined thallium 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 = .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 intravenous 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, intravenous TNG could be shown to protect ischemic myocardium in the subset of patients with smallto-moderate sized myocardial infarctions when treatment was begun within 10 hr of the onset of symptoms. The results of this trial also suggest that 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...

Platelets, vasoconstriction, and nitroglycerin during arterial wall injury. A new antithrombotic role for an old drug.

“…This hemodynamic response, which has been shown to be associated with beneficial effects in both humans and experimental animals, 18,19 required an infusion of 1,151 + 235 ,g/min nitroglycerin in the pigs. Although this rate may be higher than that usually infused in humans (and may reflect a different pharmacokinetic and pharmacodynamic profile in pigs as opposed to humans), doses up to 1,020 gg/min have been infused to achieve clinical benefit in patients.20 Ten pigs randomly assigned to nitroglycerin vehicle (n = 4, 2.4% alcohol, 2.4% propylene glycol) or 5% dextrose in water (n = 6) served as controls.…”

Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location.

“…[3][4][5][6] Experimental studies suggest that the dose might be of critical importance.78 Thus, intravenous NG therapy in low dose during the first 6 hours after coronary artery ligation reduced the size ofboth inferior7 and anterior8 infarcts, but the beneficial effects on infarct size and collateral flow were abolished when hypotension was induced by higher doses of NG. 8 An additional benefit of low-dose NG therapy over the first 6 hours of AMI in the canine model was a decrease of infarct expansion at 7 days.…”

Early detection of canine myocardial infarction by magnetic resonance imaging in vivo.

“…Drugs such as fl-blockers and nitrates have also been used early in the course of myocardial infarction in an attempt to limit infarct size. '2 3 Whether these interventions do indeed salvage reversibly ischemic myocardium is currently a subject of extensive interest and investigation. '…”