Intravenous magnesium sulfate for acute myocardial infarction
ACP J Club. 1992 Nov-Dec;117:73. doi:10.7326/ACPJC-1992-117-3-073
Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet. 1992 Jun 27;339:1553-8.
To evaluate the effectiveness of intravenous magnesium sulfate in reducing early mortality and the frequency of clinically important arrhythmias in patients with suspected myocardial infarction and in reducing the progression to acute myocardial infarction among patients with unstable coronary artery disease.
Randomized, double-blind, placebo-controlled trial.
Coronary care unit of Leicester Royal Infirmary, United Kingdom.
2316 patients (mean age, 62 y; 73% men) with suspected acute myocardial infarction with onset in the preceding 24 hours. Exclusion criteria were complete heart block; serum creatinine > 300 µmol/L; or therapeutic indication for magnesium. 16 patients (1%) were lost to follow-up.
Patients were assigned to either intravenous magnesium sulfate, 8 mmol over 5 minutes followed by 65 mmol over 24 hours (n = 1159), or to physiologic saline (n = 1157).
Main outcome measures
The primary outcome was 28-day mortality. Morbidity and treatment in the coronary care unit were also assessed.
28-day all-cause mortality was 7.8% in the magnesium group and 10.3% in the placebo group (P = 0.04), a relative reduction of 24% (95% CI, 1% to 43%). Exploratory subgroup analyses found no significant interaction between the effects of magnesium and thrombolytic treatment or aspirin, or treatment before admission with β-blocker, diuretic, nitrate, or calcium antagonist. The incidence of clinically and radiologically assessed left ventricular failure was lower in the magnesium group than in the placebo group (11.2% vs. 14.9% [P = 0.009] and 17.2% vs. 22.0% [P = 0.004], respectively). Sinus bradycardia occurred more frequently in the magnesium group than in the placebo group (10.8% vs. 8.0%; P = 0.02) as did transient flushing. Loop diuretics and sodium nitroprusside infusions were used less frequently in the magnesium group (P = 0.03), whereas atropine was used more frequently (P < 0.001). The frequency of tachyarrhythmias did not differ between the groups, and the proportion of confirmed acute myocardial infarctions was identical (65% in each group).
Intravenous magnesium sulfate, 8 mmol over 5 minutes followed by 65 mmol over 24 hours, reduces 28-day all-cause mortality in patients with suspected acute myocardial infarction.
Sources of funding: Leicestershire Health Authority and the British Heart Foundation.
For article reprint: Dr. K.L. Woods, Department of Pharmacology and Therapeutics, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
The LIMIT-2 trial triples the number of patients reported in the pooled results of the other 7 trials of intravenous magnesium for acute myocardial infarction (1). Mortality reduction in LIMIT-2 (24%) was about half that of the pooled studies (55%). LIMIT-2 differs from the other trials in several respects. In 6 of the 7 studies, serious ventricular arrhythmias were seen less often with treatment (odds ratio [OR], 0.51; CI, 0.36 to 0.73; P ≤ 0.001), whereas the groups did not differ in the LIMIT-2 trial. Heart failure, vaguely defined and reported in 5 trials, was 9.0% in the placebo group and 6.7% in the magnesium group (OR, 0.73; CI, 0.41 to 1.30), whereas both clinically and radiologically defined acute left ventricular failure was twice as common and was significantly reduced by magnesium in the LIMIT-2 study. One smaller study suggested decreased progression to infarction; another study suggested a smaller infarct size after magnesium. Neither finding was seen in LIMIT-2. LIMIT-2 findings suggest a safe and worthwhile benefit of intravenous magnesium in patients with strongly suspected acute myocardial infarction, and subgroup analysis showed no interaction with aspirin or thrombolytic agents. The study did not address interactions with other agents more likely to lower blood pressure, such as intravenous β-blockers or nitrates, both of which may reduce mortality. Because subgroup analyses differed from findings in other trials, LIMIT-2 did not clarify the mechanism of action of magnesium.
Routine use of intravenous magnesium for suspected acute myocardial infarction can be strongly considered, but its comparative priority and place in combination with other drugs remains to be established. It should be noted that investigators of the ISIS-4 trial of intravenous magnesium, oral captopril, and oral mononitrate for suspected acute myocardial infarction elected to continue patient recruitment after reviewing the LIMIT-2 trial, in part because the wide confidence interval of LIMIT-2 left definitive recommendations in question.
Steven Borzak, MD
Henry Ford Heart and Vascular Institute Detroit, Michigan