PMID- 17387132
OWN - NLM
STAT- MEDLINE
DCOM- 20070425
LR  - 20161017
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 297
IP  - 15
DP  - 2007 Apr 18
TI  - Effect of tilarginine acetate in patients with acute myocardial infarction and 
      cardiogenic shock: the TRIUMPH randomized controlled trial.
PG  - 1657-66
AB  - CONTEXT: Cardiogenic shock complicating acute myocardial infarction (MI) remains 
      a common and lethal disorder despite aggressive use of early revascularization. 
      Systemic inflammation, including expression of inducible nitric oxide synthase 
      (NOS) and generation of excess nitric oxide, is believed to contribute to the 
      pathogenesis and inappropriate vasodilatation of persistent cardiogenic shock. 
      Preliminary, single-center studies suggested a beneficial effect of NOS 
      inhibition on hemodynamics, renal function, and survival in patients with 
      cardiogenic shock. OBJECTIVE: To examine the effects of an isoform-nonselective 
      NOS inhibitor in patients with MI and refractory cardiogenic shock despite 
      establishment of an open infarct artery. DESIGN, SETTING, AND PATIENTS: 
      International, multicenter, randomized, double-blind, placebo-controlled trial 
      (Tilarginine Acetate Injection in a Randomized International Study in Unstable MI 
      Patients With Cardiogenic Shock [TRIUMPH]) with planned enrollment of 658 
      patients at 130 centers. Participants were enrolled between January 2005 and 
      August 2006 when the study was terminated early. INTERVENTION: Tilarginine 
      (L-N(G)-monomethylarginine [L-NMMA]), 1-mg/kg bolus and 1-mg/kg per hour 5-hour 
      infusion, vs matching placebo. MAIN OUTCOME MEASURES: The primary outcome was 
      30-day all-cause mortality among patients who received study medication. 
      Secondary outcomes included shock resolution and duration, New York Heart 
      Association (NYHA) functional class at 30 days, and 6-month mortality. RESULTS: 
      Enrollment was terminated at 398 patients based on a prespecified futility 
      analysis. Six-month follow-up was completed in February 2007. There was no 
      difference in 30-day all-cause mortality between patients who received 
      tilarginine (97/201 [48%]) vs placebo (76/180 [42%]) (risk ratio, 1.14; 95% 
      confidence interval, 0.92-1.41; P = .24). Resolution of shock (133/201 [66%] 
      tilarginine vs 110/180 [61%] placebo; P = .31) and duration of shock (median, 156 
      [interquartile range, 78-759] hours tilarginine vs 190 [100-759] placebo; P = 
      .16) were similar. At 30 days a similar percentage of patients had heart failure 
      (48% tilarginine vs 51% placebo; P = .51) with a similar percentage of those 
      patients in NYHA class I/II (73% tilarginine vs 75% placebo; P = .27). After 6 
      months mortality rates were similar in the 2 groups (58% tilarginine vs 59% 
      placebo; hazard ratio, 1.04; 95% confidence interval, 0.79-1.36; P = .80). 
      CONCLUSIONS: Tilarginine, 1-mg/kg bolus and 5-hour infusion, did not reduce 
      mortality rates in patients with refractory cardiogenic shock complicating MI 
      despite an open infarct artery. Early mortality rates in this patient group are 
      high. Further research is needed to develop effective therapies for patients with 
      cardiogenic shock following acute MI. TRIAL REGISTRATION: clinicaltrials.gov 
      Identifier: NCT00112281
CN  - TRIUMPH Investigators
AD  - Duke University, Durham, NC, USa.
FAU - Alexander, John H
AU  - Alexander JH
FAU - Reynolds, Harmony R
AU  - Reynolds HR
FAU - Stebbins, Amanda L
AU  - Stebbins AL
FAU - Dzavik, Vladimir
AU  - Dzavik V
FAU - Harrington, Robert A
AU  - Harrington RA
FAU - Van de Werf, Frans
AU  - Van de Werf F
FAU - Hochman, Judith S
AU  - Hochman JS
LA  - eng
SI  - ClinicalTrials.gov/NCT00112281
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070326
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (N(G)-monomethylarginine acetate)
RN  - 0 (Protein Isoforms)
RN  - 0 (Vasoconstrictor Agents)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
CIN - JAMA. 2007 Apr 18;297(15):1711-3. PMID: 17440148
CIN - JAMA. 2007 Sep 5;298(9):971-2; author reply 972-3. PMID: 17785640
CIN - JAMA. 2007 Sep 5;298(9):971; author reply 972-3. PMID: 17785641
MH  - Aged
MH  - Arginine/adverse effects/*analogs & derivatives/therapeutic use
MH  - Blood Pressure
MH  - Double-Blind Method
MH  - Enzyme Inhibitors/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/*drug therapy
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Prospective Studies
MH  - Protein Isoforms
MH  - Shock, Cardiogenic/*drug therapy
MH  - Vascular Patency
MH  - Vasoconstrictor Agents/adverse effects/*therapeutic use
EDAT- 2007/03/28 09:00
MHDA- 2007/04/26 09:00
CRDT- 2007/03/28 09:00
PHST- 2007/03/28 09:00 [pubmed]
PHST- 2007/04/26 09:00 [medline]
PHST- 2007/03/28 09:00 [entrez]
AID - 297.15.joc70035 [pii]
AID - 10.1001/jama.297.15.joc70035 [doi]
PST - ppublish
SO  - JAMA. 2007 Apr 18;297(15):1657-66. doi: 10.1001/jama.297.15.joc70035. Epub 2007 
      Mar 26.