L-Arginine After MI Linked to Higher Mortality


The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to increased postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy. “The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE inhibitors to improve vascular function.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function.”

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