A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty

doi:10.1067/mhj.2000.110767

American Heart Journal

Volume 140, Issue 6, December 2000, Pages 891-897

https://doi.org/10.1067/mhj.2000.110767 Get rights and content

Abstract

Background Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction. Methods One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat. Results There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 ± 0.61 vs 1.85 ± 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% ± 11% vs 50% ± 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 ± 2359 vs 2404 ± 1673,P =.052). Conclusions Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty. (Am Heart J 2000;140:891-7.)

Section snippets

Study population

Patients of any age were eligible when all the following inclusion criteria were fulfilled: (1) chest pain of >30 minutes’ duration associated with ≥0.1 mV ST-segment elevation in ≥2 contiguous electrocardiographic leads, (2) admission to the coronary care unit within 6 hours of symptom onset, (3) good acoustic window, and (4) no planned inclusion in other trials. Exclusion criteria were cardiogenic shock or severe hypotension with systolic blood pressure <90 mm Hg, sinus bradycardia <50

Randomization, treatment, and 30-day follow-up

Out of 183 consecutive screened patients, 150 (82%) were randomized. Reasons for nonrandomization of the remaining 33 are shown in Figure 1.

. Trial profile. AMI, Acute myocardial infarction.

Characteristics of the randomized patients are reported in Table I.Demographic and clinical characteristics, time from symptom onset to randomization, baseline echocardiography, and coronary angiography and procedural data of the two randomized groups did not show significant differences. The baseline mean

Discussion

Our study included a small sample of patients but its features were well suited to assess the hypothesis of a protective effect of magnesium against reperfusion injury. The infarct-related vessel was found completely occluded or with a markedly reduced anterograde flow (TIMI grade 0-1 flow) in 79% of the patients. The collateral flow to the infarct area was absent or poor (Rentrop grade 0-1) in 89% of the subjects. Coronary angioplasty was effective in 99% of the treated patients in reopening

References (24)

J Leor et al.
An experimental model examining the role of magnesium in the therapy of acute myocardial infarction
Am J Cardiol
(1995)
LFM Barros et al.
Magnesium treatment of acute myocardial infarction: effects on necrosis in an occlusion/reperfusion dog model
Int J Cardiol
(1995)
RA Kloner
Does reperfusion injury exist in humans?
J Am Coll Cardiol
(1993)
KL Woods et al.
Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)
Lancet
(1992)
KL Woods et al.
Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)
Lancet
(1994)
KL Woods
Mega-trials and management of acute myocardial infarction
Lancet
(1995)
GF Baxter et al.
Infarct size and magnesium: insights into LIMIT-2 and ISIS-4 from experimental studies
Lancet
(1996)
L Bolognese et al.
Myocardial contrast echocardiography versus dobutamine echocardiography for predicting functional recovery after acute myocardial infarction treated with primary coronary angioplasty
J Am Coll Cardiol
(1996)
D Antoniucci et al.
A clinical trial comparing primay stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction: results from the Florence randomized elective stenting in acute coronary occlusions (FRESCO) trial
J Am Coll Cardiol
(1998)
J Oh et al.
Correlation of regional wall motion abnormalities detected by two-dimensional echocardiography with perfusion defect determined by technetium 99m sestamibi imaging in patients treated with reperfusion therapy during acute myocardial infarction
Am Heart J
(1996)

CW Christensen et al.

Magnesium sulfate reduces myocardial infarct size when administered prior to but not after coronary reperfusion in a canine model

Circulation

(1995)

WR Herzog et al.

Timing of magnesium therapy affects experimental infarct size

Circulation

(1995)

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^☆: Reprint requests: Giovanni M. Santoro, MD, Cardiology I, Careggi Hospital, Viale Morgagni 85, 50134 Florence, Italy. E-mail: [email protected]

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Interventional CardiologyA randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty☆

Abstract

Section snippets

Study population

Randomization, treatment, and 30-day follow-up

Discussion

Am J Cardiol

Int J Cardiol

J Am Coll Cardiol

Lancet

Lancet

Lancet

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

Magnesium sulfate reduces myocardial infarct size when administered prior to but not after coronary reperfusion in a canine model

Circulation

Timing of magnesium therapy affects experimental infarct size

Circulation

Interventional Cardiology
A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty☆