Protective effect of intravenous magnesium in acute myocardial infarction following thrombolytic therapy

Abstract

The role of intravenous magnesium therapy in patients with acute myocardial infarction (AMI) who received thrombolytic therapy is controversial. The results from previous clinical trials were not in consonance. We therefore conducted a prospective, randomized, double-blind, placebo controlled study in 350 patients with confirmed AMI during the period January 1994 to December 1996. The role of intravenous magnesium sulphate therapy (2 g over 5 min followed by 16 g over 24 h) was evaluated in patients with AMI who received thrombolytic therapy. Study group consisted of 169 patients who were administered magnesium sulphate. Control group comprised of 181 patients who were given isotonic saline. Among those in the magnesium group, 70% received magnesium within 6 h after the onset of symptoms. All patients received magnesium immediately after the completion of thrombolytic therapy. Patients were followed up for 30 days after AMI.

The number of deaths in the study group was 6 (3.5%) compared with control arm in which 18 patients (9.9%) died (P value <0.01 95% Confidence intervals [CI] 1.2 to 11.6). Ventricular arrhythmias were also less in the magnesium arm; 27 patients [13%]) compared with 83 patients (48.6%) in the control arm (P value 0.00001 95% Cl 26.7 to 44.5). In the magnesium group 15 patients (8.8%) had re-infarction compared with 23 patients (12.7%) in the placebo arm (P value not significant). Post myocardial infarction angina was observed in 47 patients (27.8%) in the magnesium arm compared with 60 patients (33.1%) in the placebo arm (P value not significant). The main side effect of intravenous magnesium was transient flushing observed in 152 (90%) patients. Intravenous magnesium sulphate in patients with AMI is a safe and useful adjunct to thrombolytic therapy in reducing the short-term mortality and ventricular arrhythmias after AMI.

Introduction

The value of routine therapy with intravenous magnesium sulphate in patients with acute myocardial infarction (AMI) is controversial. Magnesium has been reported to protect myocardial tissue in experimental models of ischemia and reperfusion injury [1]. Several small randomized trials reported the benefit of magnesium in patients with AM1 [2], [3], [4], [5], [6]. A meta-analysis of these trials [7] also demonstrated an overall beneficial effect of magnesium administration in AMI patients but two subsequent large clinical trials showed divergent results. In the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) [8] a 24% reduction in the 28-day mortality was shown, whereas the fourth International Study of Infarct Survival (ISIS-4) [9] showed no benefit. A major drawback of these studies was a significant number of the patients recruited did not receive thrombolytic therapy. As a result, there is no consensus among the clinicians that magnesium is beneficial in patients with AMI who received thrombolytic therapy.

Magnesium is a cofactor of numerous enzymatic reactions that are central to cellular homeostasis. It has been shown that intracellular magnesium concentrations are lower than normal during the first 24 h after AMI [10]. It is during this period that maximum ischemic myocardial damage occurs, which is associated with increased morbidity and mortality. Infusion of magnesium early after the onset of AMI may reduce the extent of ischemic myocardial damage and thus may reduce the morbidity and mortality [11]. Magnesium sulphate may lower systemic vascular resistance, dilate coronary arteries [12], improve myocardial metabolism [13], reduce platelet aggregation [14], stabilize cell membranes [15] and protect against catecholamine-induced myocardial necrosis [16].

The purpose of our study was to evaluate the potential benefits of early magnesium sulphate administration in patients with AMI who received thrombolytic therapy. We studied the effect of this therapy on the incidence of early mortality, ventricular arrhythmias, early re-infarction and post-infarction angina.