Nitric oxide inhibition rapidly increases blood pressure with no change in outcome in cardiogenic shock: the TRIUMPH trial.
The TRIUMPH study, recently published in Journal of the American Medical Association, was a prospective randomized placebo-controlled trial testing the hypothesis that tilarginine (a non-specific inhibitor of nitric oxide synthase), when compared with placebo, would reduce 30-day mortality by 25% in patients with myocardial infarction complicated by refractory cardiogenic shock despite successful revascularization of the infarct-related artery. Patients received an intravenous bolus of the drug followed by 5 hours of intravenous infusion of the drug or a matching placebo. Although tilarginine increased systolic blood pressure by 5 mmHg at 2 hours, no effect on mortality was observed at 30 days. There was, however, a 6% absolute increase in 30-day mortality in the tilarginine group (48%, versus 42% in the placebo). This definitive trial gave strong indications for stopping any further trial using non-specific inhibitors of nitric oxide synthase in cardiogenic shock and possibly also in any other cardiovascular area.
Salem
Réda
R
Département de Cardiologie, Centre Hospitalier de l'université de Montréal, 3840 rue Saint-Urbain Montréal (Québec)H2W 1T8, Canada.
Mebazaa
Alexandre
A
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D011446:Prospective Studies; D012770:Shock, Cardiogenic / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome; D019323:omega-N-Methylarginine
D001120:Arginine; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine