In Reply: Dr Kielstein and colleagues speculate that higher baseline levels of the endogenous NOS inhibitor ADMA in patients with renal dysfunction might explain the nonstatistically significant interaction suggesting harm with L-NMMA in patients with higher baseline creatinine levels in TRIUMPH and the negative result overall in the trial. Our understanding of these data is limited by the absence of renal function data prior to the development of shock. In addition, patients in cardiogenic shock have abnormal and unstable renal function, so accurate estimation of baseline renal function is impossible. Furthermore, the preliminary single-center studies that found benefit of NOS inhibition in cardiogenic shock included patients with levels of renal dysfunction that were similar to TRIUMPH.1,2
Harrington RA, Alexander JH, Hochman JS, Reynolds HR, Dzavik V, Van de Werf FJ. Tilarginine in Patients With Acute Myocardial Infarction and Cardiogenic Shock—Reply. JAMA. 2007;298(9):971–973. doi:10.1001/jama.298.9.972
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