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January 21, 2006
By: Sahar Bedrood B.S. and Asher Kimchi M.D.
Baltimore, MD - The amino acid L-arginine, the substrate for nitric oxide synthase (NOS), has been publicized as being beneficial for hypertension, angina and heart failure. Steven Shulman M.D., et al from John Hopkins Hospital investigated L-arginine’s efficacy in patients who experienced ST-segment elevation myocardial infarction (STEMI). Thus, the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) was designed to test whether the administration of L-arginine would decrease vascular stiffness and improve left ventricular function during the 6-month period following a patient’s first STEMI. The results, published in the January 4, 2006 issue of the Journal of American Medical Association, indicated L-arginine does not improve vascular stiffness measurements or ejection fraction and may be associated with higher post-infarction mortality.
The study consisted of a double-blind, randomized, placebo-controlled trial to test the efficacy of L-arginine is a total of 153 patients following a first ST-segment elevation myocardial infarction. Patients were randomly assigned to receive L-arginine with a goal dose of 3 g 3 times a day or a matching placebo for 6 months.
There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either the group of patients who received L-arginine or the placebo group. However, 6 participants (8.6%) in the L-arginine group died during the 6-month study period vs. none in the placebo group (p= 0.01).
In this study, 6 months of L-arginine therapy failed to decrease vascular stiffness measurements. The increased number of mortalities with L-arginine therapy compared to placebo may be explained by the generation of reactive oxygen species instead of nitric oxide. This generation could then lead to many consequences, such as metalloprotease production, fetal gene _expression and left ventricular dilation which could all result in pressure overload.
In conclusion, L-arginine therapy should not be given to patients following myocardial infarction. It does not improve vascular stiffness nor improves left ventricular function. In some cases, L-arginine may worsen clinical outcomes.
Co-authors: Steven P. Shulman MD; Lewis C. Becker, MD; David Kass, MD; Hunter Champion, MD, PhD; Michael L. Terrin, MD, Sandra Forman, MA; Kavita V. Ernst, MD; Mark D. Keleman, MD; Susan N. Townsend, RN, BS; Anne Caprioti, Joshua M. Hare, MD; Gary Gerstenblith, MD
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