No TRIUMPH for Tilarginine ▸

Cardiogenic shock carries a mortality rate in excess of 50%. Induction of nitric oxide synthase (NOS), leading to the generation of excess nitric oxide, is believed to contribute to the inappropriate vasodilatation seen in cardiogenic shock. Tilarginine acts as an NOS inhibitor and early studies have suggested a potential clinical benefit. The TRIUMPH (Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock) planned to enrol 658 patients at 130 centres, however the study was terminated early after 398 patients had been enrolled. All patients were in refractory cardiogenic shock after myocardial infarction (MI) despite revascularisation. The primary outcome was all-cause mortality among patients who received the study drug. Secondary outcomes included shock resolution and duration, NYHA class at 30 days, and 6-month mortality. Enrolment was stopped in August 2006 and the 6-month follow-up completed in February 2007. No difference in 30-day all-cause mortality was found between patients who received tilarginine (48%) and those who received placebo (42%; p = 0.24). Resolution of shock (66% for tilarginine, 61% for placebo; p = 0.31) and duration of shock (156 vs 190 hours; p = 0.16) were similar. At 30 days a similar percentage of patients had heart failure (48% tilarginine vs 51% placebo; p = 0.51), with a similar percentage of patients in NYHA class I/II (73% tilarginine vs 75% placebo; p = 0.27). After 6 months, mortality rates were similar in the two groups (58% tilarginine vs 59% placebo; p = 0.80). Tilarginine did not reduce mortality rates in patients with refractory cardiogenic shock complicating MI despite an open infarct artery. It should be borne in mind that in this trial the drug was given late once shock was established; NOS inhibition might still theoretically have an important role if given at an earlier stage.

▴ The TRIUMPH Investigators. Effect of tilarginine acetate in patients with acute … OpenUrlCrossRefPubMedWeb of Science