Vascular Interaction With Age in Myocardial Infarction - VINTAGE-MI


The goal of the trial was to evaluate the effect of addition of the amino acid L-arginine to standard postinfarction therapy on vascular stiffness and ejection fraction in patients with ST elevation myocardial infarction (STEMI).

Study Design

Study Design:

Patients Enrolled: 153
Mean Follow Up: 6 months
Mean Patient Age: Mean age 60 years
Female: 32

Patient Populations:

Age ≥30 years; first STEMI within prior 3-21 days.


Prior documented Q-wave MI, present cardiogenic shock, active acute coronary syndrome, severe underlying noncardiac disease limiting predicted life span to <1 year, poorly controlled diabetes, or significant renal or hepatic disease

Primary Endpoints:

Change in gated blood pool–derived ejection fraction over 6 months in patients age ≥60 years

Secondary Endpoints:

Change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events.

Drug/Procedures Used:

Patients were randomized in a double-blind manner a mean of 5.9 days following admission for STEMI to either L-arginine (target dose 3 g three times daily; n=78) or placebo (n=75) for 6 months. Vascular and ventricular function evaluation was performed at baseline and 6 months. All other post-infarction medications were maintained in the usual manner.

Concomitant Medications:

Aspirin 100%, clopidogrel 90%, ACE Inhibitor 91%, beta blocker 94%, HMG CoA reductase inhibitor 97%

Principal Findings:

Baseline characteristics were well balanced between treatment groups. The cohort for the primary analysis, patients age ≥60 years, made up 50% of the study (n=77). The majority of patients were treated with PCI (88%), with initial TIMI Flow Grade 0 or 1 in 60% of these patients and final TIMI Flow Grade of 3 in 82% of patients. The trial was discontinued early at the recommendation of the data safety monitoring board due to increased mortality in the L-arginine group. Six month data were completed in 114 patients.

There was no difference in the primary endpoint of change from baseline in 6 month ejection fraction between treatment groups in the ≥60 year old cohort (-1.0% each, p=0.63) or the overall population (+0.8% for L-arginine vs -0.4% for placebo). Likewise, there was no difference in six month pulse pressure (51.6 mm Hg for L-arginine vs 54.8 mm Hg for placebo), arterial elastance (1.5 mm Hg/mL in each group), or radial artery compliance (2.0 mL/mm Hg and 1.8 mL/mm Hg, respectively). Mortality at six months was higher in the L-arginine group (n=6; 8.6% vs 0%, p=0.01), as was the composite of death, myocardial infarction and hospitalization for heart failure (16.7% vs 10.1%). The majority of the fatal events were in the ≥ age 60 years cohort (n=5).


Among patients with ST elevation MI, treatment with the amino acid L-arginine in addition to standard postinfarction therapy was not associated with a difference in the primary endpoint of change in ejection fraction at six months compared with placebo, but was associated with an increase in mortality, which prompted the trial to be stopped early.

The majority of the fatal events were among patients age ≥60 years who were in the L-arginine group. The authors suggest this may be explained in part to increased endothelial dysfunction in older post-MI patients, which may be enhanced with the addition of L-arginine as it acts as a substrate for the endothelial-specific isoform of nitric oxide synthase (eNOS).


Schulman SP, et al. L-Arginine Therapy in Acute Myocardial Infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial. JAMA 2006;295 58-64.

Clinical Topics: Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure

Keywords: Coronary Artery Disease, Myocardial Infarction, Protein Isoforms, Radial Artery, Nitric Oxide Synthase, Heart Failure, Clinical Trials Data Monitoring Committees, Ventricular Function, Blood Pressure, Vascular Stiffness

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