Efficacy and safety of oral l-arginine in acute myocardial infarction. Results of the multicenter, randomized, double-blind, placebo-controlled ARAMI pilot trial.

AIMS: L-arginine is a substrate for nitric oxide (NO) synthesis in vascular endothelial cells. NO bioavailability is decreased during myocardial infarction (MI). It might be expected that administration of L-arginine may maintain NO production and alleviate the course of MI. The aim of the study was to assess safety and effects of treatment with L-arginine on the clinical course of MI. METHODS AND RESULTS: 792 patients (mean age 64 years, 551 men) with ST segment elevation MI admitted within 24h after the onset of symptoms were randomized to oral L-arginine (3.0 t.i.d p.o. for 30 days) or placebo on top of routine therapy. The end point which was the composite of 30 day cardiovascular death, reinfarction, successful resuscitation, shock/pulmonary edema or recurrent myocardial ischemia occurred in 24% patients treated with L-arginine and 27% with placebo (OR 0.63, 95% CI 0.39-1.02, p=0.06). The end point was observed less frequently in 226 patients with hyperlipidemia (19 vs 31, p<0.05). No serious adverse effects were observed during L-arginine supplementation. CONCLUSIONS: This study, which is the first attempt to use L-arginine in MI, showed that oral L-arginine supplementation was well tolerated. Beneficial nonsignificant trend was observed towards reduction of major clinical events.

Antioxidant effects of combined vitamins C and E in acute myocardial infarction. The randomized, double-blind, placebo controlled, multicenter pilot Myocardial Infarction and VITamins (MIVIT) trial.

AIMS: There is a large body of evidence that reactive oxygen species (ROS) produced during myocardial ischemia and reperfusion play a crucial role in myocardial damage and endothelial dysfunction. The MIVIT pilot trial was designed to test the effects of antioxidant vitamins C and E on the clinical outcome of patients with AMI. METHODS AND RESULTS: In this randomized, double-blind, multicenter trial, 800 patients (mean age 62) with AMI were randomly allocated to receive, on top of routine medication, one of two treatments: vitamin C (1000 mg/12 h infusion) followed by 1200 mg/24 h orally and vitamin E (600 mg/24 h) or matching placebo for 30 days. Primary end point (composite of in-hospital cardiac mortality, non-fatal new myocardial infarction, VT/VF/asystole, shock/pulmonary edema) occurred less frequently in patients treated with antioxidants (55 [14%] vs 75 [19%], OR 0.82 [95% CI, 0.68-1.00], p=0.048). CONCLUSIONS: This randomized pilot trial shows that supplementation with antioxidant vitamins is safe and seems to positively influence the clinical outcome of patients with AMI. A larger study is warranted to provide further evidence of this promising and inexpensive regimen.