Cardiovascular diseases (CVD) are the main cause of death in the UK, accounting for almost 200,000 deaths per year. One of the manifestations of CVD is acute myocardial infarction (MI or heart attack). There are estimated to be approximately 125,000 acute MIs in the UK per year. Whilst early reperfusion (restoring of blood flow to the heart) plays an important role in reducing the infarct size (area of dead tissue resulting from failure of blood supply), the reperfusion process itself causes injury. Effective therapy aimed at reducing this reperfusion injury has the potential to substantially to reduce the risk of developing heart failure after an MI. There is evidence from animal models to suggest that an injection of sodium nitrite prior to reperfusion may reduce the reperfusion injury.
NIAMI is a multi-centre, double-blind, randomised trial, funded by the MRC, evaluating sodium nitrite injection versus placebo. The primary outcome is the difference in final infarct size between sodium nitrite and placebo groups measured using Magnetic Resonance Imaging (MRI) 6-8 days following the acute myocardial infarction and corrected for area at risk. Secondary endpoints include plasma creatine kinase and Troponin I over 72 hours and LV ejection fraction and LV end systolic volume index at 10-14 days and 6 months.
The inclusion criteria were: men aged ≥18 years, women aged ≥55 years and women aged <55 years (of childbearing potential who are sterilised, or have had a hysterectomy or have effective contraception); presenting within 12 hours of the onset of chest pain who have ST segment elevation of more than 1mm elevation in limb leads or 2mm elevation in two contiguous chest leads with occlusion of the culprit related artery (TIMI grade 0 or TIMI grade 1) for whom the clinical decision has been made to treat with primary percutaneous coronary intervention (PCI). A total of 229 patients were recruited and randomised to either 5ml low-dose sodium nitrite or saline (placebo) given intravenously over 5 minutes immediately prior to the primary PCI.
There was no difference in myocardial infarct size at 6-8 days 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. The study concluded that intravenous sodium nitrite administered immediately prior to reperfusion in patients with acute STEMI did not reduce infarct size.
The results have been published in the European Heart Journal, doi:10.1093/eurheartj/ehu096 http://eurheartj.oxfordjournals.org/content/early/2014/03/16/eurheartj.ehu096
Protocol paper: http://www.translational-medicine.com/content/11/1/116