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

Abstract

Aim: Despite 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 double-blind 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 results: A 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.

Conclusions: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.

Keywords: Acute myocardial infarction; Cardioprotection; Ischaemia-reperfusion injury; Nitrite.

Figure 1

CONSORT diagram.

Figure 2

Relation between infarct size (late gadolinium enhancement planimetry on early scan) and area at risk (late gadolinium enhancement endocardial surface area (ESA) technique on early scan) in nitrite and placebo groups (upper panel). Serial measures of mean total creatine kinase and Troponin I immediately prior to and over 72 h following administration of nitrite and placebo. Nitrite did not significantly reduce the area under the curve for either biomarker (lower panel).