Author Affiliations: Division of Cardiology (Drs Schulman, Becker, Kass, Champion, Ernst, Kelemen, Hare, and Gerstenblith and Mss Townsend and Capriotti), Johns Hopkins Medical Institutions, and Maryland Medical Research Institute (Dr Terrin and Ms Forman), Baltimore. Dr Terrin is now at the Department of Epidemiology and Dr Kelemen is at the Division of Cardiology, University of Maryland School of Medicine, Baltimore, and Dr Ernst is now at the Division of Cardiology, Stanford School of Medicine, Stanford, Calif.
Context The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L-arginine has the potential to reduce vascular stiffness.
Objective To determine whether the addition of L-arginine to standard postinfarction therapy reduces vascular stiffness and improves ejection fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction.
Design and Setting Single-center, randomized, double-blind, placebo-controlled trial with enrollment from February 2002 to June 2004.
Patients A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older.
Intervention Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months.
Main Outcome Measures Change in gated blood pool–derived ejection fraction over 6 months in patients 60 years or older randomized to receive L-arginine compared with those assigned to receive placebo. Secondary outcomes included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events.
Results Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or L-arginine. The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study 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 = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment.
Conclusions L-Arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-Arginine should not be recommended following acute myocardial infarction.
Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00051376
Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G. L-Arginine Therapy in Acute Myocardial InfarctionThe Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial. JAMA. 2006;295(1):58–64. doi:10.1001/jama.295.1.58