L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial

JAMA. 2006 Jan 4;295(1):58-64. doi: 10.1001/jama.295.1.58.


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, NCT00051376.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Arginine / adverse effects
  • Arginine / therapeutic use*
  • Atherosclerosis
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Stroke Volume / drug effects
  • Ventricular Function, Left / drug effects*


  • Arginine

Associated data

  • ClinicalTrials.gov/NCT00051376