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The role of magnesium as antithrombotic therapy
1Heart Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel. shechtes@netvision.net.il
Insights
Magnesium supplementation may reduce mortality in acute myocardial infarction (AMI) patients. Oral magnesium also inhibits thrombus formation in coronary artery disease (CAD), offering a potential therapeutic benefit.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pharmacology
Background:
- Meta-analysis showed intravenous magnesium reduced mortality and complications in acute myocardial infarction (AMI).
- This suggests magnesium may inhibit thrombosis in coronary artery disease (CAD).
Purpose of the Study:
- To investigate the effect of oral magnesium on platelet-dependent thrombosis in stable CAD patients.
- To explore the molecular mechanisms underlying magnesium's antithrombotic effects.
Main Methods:
- Prospective, double-blind, crossover study in stable CAD patients.
- Measured platelet-dependent thrombosis inhibition and platelet aggregation.
- Assessed effects on thromboxane A2, prostacyclin, and nitric oxide synthesis.
Main Results:
- Oral magnesium inhibited thrombus formation by 35% in CAD patients, independent of platelet aggregation.
- Magnesium's antithrombotic effect was additive to aspirin.
- Magnesium inhibited platelet aggregation agonists and stimulated prostacyclin synthesis, likely via reduced intracellular calcium.
- Hypomagnesemia impaired nitric oxide release, potentially promoting vasoconstriction and thrombosis.
Conclusions:
- Magnesium treatment inhibits platelet-dependent thrombosis in CAD patients.
- Magnesium may improve endothelial function and vasodilation.
- These findings suggest a mechanism for magnesium's benefit in CAD outcomes.
Abstract:
Meta-analysis of previous relatively small clinical trials, comparing intravenous magnesium with placebo in acute myocardial infarction (AMI) patients, mainly without thrombolytic therapy, demonstrated that magnesium reduced in-hospital mortality by 19%, mainly by reducing the incidence of serious arrhythmias and left ventricular heart failure by one quarter. These findings have led us to hypothesize that magnesium treatment inhibits platelet-dependent thrombosis in patients with coronary artery disease (CAD). In a prospective, double blind, and crossover study, we have recently demonstrated that oral magnesium treatment inhibits thrombus formation measured by platelet-dependent thrombosis in stable CAD patients by 35%. This effect appears to be independent of platelet aggregation and activation, and is additive to that of aspirin. High dose of intravenous magnesium can inhibit thrombus formation and is associated with suppression of platelet aggregation. Magnesium treatment can dose-dependently inhibit a wide variety of agonists of platelet aggregation, such as thromboxane A2 and stimulate prostacyclin synthesis. The molecular basis for these effects is likely modulated via reduction of intracellular calcium mobilization. Hypomagnesemia also selectively impaired the release of nitric oxide from the coronary endothelium. We have recently demonstrated that oral magnesium treatment can improve endothelium-dependent vasodilation in CAD patients with optimal lipid values. Because nitric oxide is a potent endogenous vasodilator and inhibitor of platelet aggregation and adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis in hypomagnesemic states. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in CAD patients.