Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI)

Abstract

AimDespite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this doubleblind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).Methods and resultsA total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6–8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6–8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size −0.7% 95% CI: −2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6–8 days and at 6 months and final infarct size (FIS) measured at 6 months.ConclusionsSodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.

The Coronary Circulation as a Target of Cardioprotection

“…31,231,232 Intravenous nitrite in patients with ST-segment elevation myocardial infarction and interventional reperfusion failed to reduce infarct size (biomarker and MRI) or to affect TIMI flow (angiography). 233 Intracoronary nitrite in patients with ST-segment elevation myocardial infarction and interventional reperfusion reduced infarct size (creatine kinase and MRI) only in a subgroup of patients with TIMI flow ≤1 at admission, and in this subgroup, intracoronary nitrite also reduced the area of microvascular obstruction (MRI). 234 Erythropoietin in patients with STsegment elevation myocardial infarction and interventional reperfusion neither reduced infarct size (creatine kinase and MRI) nor improved TIMI flow.…”

Molecular Basis of Cardioprotection

“…36 In contrast to the positive clinical studies with mechanical conditioning strategies, studies attempting to recruit cardioprotective signals pharmacologically have largely failed, including those on adenosine, [495][496][497][498] on PKCδ inhibition, 188 and on intravenous nitrite which is bio-converted to NO. 499 Erythropoietin failed to reduce IS in 2 trials, 501,502 but there was no evidence before that erythropoietin participated in the conditioning phenomena. One study on atrial natriuretic peptide demonstrated modest IS reduction, but atrial natriuretic peptide is not really an endogenous trigger or mediator of conditioning.…”

Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation

“…Nitrite therapy is a rapidly expanding area with great potential for improved clinical outcome in patients, however caution is advised in the translation of results obtained in animal experimental models to the clinical setting. A recent multi-centre, double-blind, placebo controlled clinical trial showed that nitrite was ineffective when administered intravenously immediately prior to PPCI in patients presenting with first acute STEMI (Siddiqi et al, 2014). Therefore, we need to be mindful of differences between animal and human physiology as well as inter-individual differences in responsiveness to nitrite between subjects.…”