Randomized Phase 2 Trial of Intra-Coronary Nitrite During Acute Myocardial Infarction

TY - JOUR

T1 - Randomized Phase 2 Trial of Intra-Coronary Nitrite During Acute Myocardial Infarction

AU - Jones, Daniel A

AU - Pellaton, Cyril

AU - Velmurugan, Shanti

AU - Andiapen, Mervyn

AU - Antoniou, Sotiris

AU - van Eijl, Sven

AU - Webb, Andrew J

AU - Westwood, Mark

AU - Parmar, Mahesh

AU - Mathur, Anthony

AU - Ahluwalia, Amrita

PY - 2015/1/30

Y1 - 2015/1/30

N2 - Rationale: Pre-clinical evidence demonstrates that inorganic nitrite, following its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective: We investigated whether intra-coronary injection of nitrite during primary percutaneous coronary intervention (PCI) might improve infarct size in ST-elevated myocardial infarction (STEMI). Methods and Results: Patients undergoing primary PCI (n=80) were randomised to receive intracoronary (10mL) sodium nitrite (1.8μmol) or NaCl (placebo) before balloon inflation. The primary endpoint was infarct size assessed by measuring creatine kinase (CK) release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac magnetic resonance imaging (CMR) on day 2. Baseline characteristics were similar between the groups. No evidence of differences in CK release (p=0.92), troponin T (p=0.85) or CMR-assessed infarct size (p=0.254) were evident. In contrast there was a reduction in myocardial salvage index (p=0.05) and MACE at 1 year (2.6% vs 15.8%, p=0.04) in the nitrite group. In a 66-patient sub-group with TIMI≤1 flow there was reduced serum CK (p=0.030) and a 19% reduction in CMR-determined infarct size (p=0.034) with nitrite. No adverse effects of nitrite were detected.Conclusions: In this phase II study intra-coronary nitrite infusion did not alter infarct size although a trend to improved myocardial salvage index and a significant reduction in MACE was evident. In a sub-group of patients with TIMI flow≤1 nitrite reduced infarct size and MACE and improved myocardial salvage index indicating that a phase III clinical trial assessing intra-coronary nitrite administration as an adjunct to PCI in STEMI patients is warranted. Clinical Trial Registration: http://clinicaltrials.gov - NCT01584453.

AB - Rationale: Pre-clinical evidence demonstrates that inorganic nitrite, following its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective: We investigated whether intra-coronary injection of nitrite during primary percutaneous coronary intervention (PCI) might improve infarct size in ST-elevated myocardial infarction (STEMI). Methods and Results: Patients undergoing primary PCI (n=80) were randomised to receive intracoronary (10mL) sodium nitrite (1.8μmol) or NaCl (placebo) before balloon inflation. The primary endpoint was infarct size assessed by measuring creatine kinase (CK) release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac magnetic resonance imaging (CMR) on day 2. Baseline characteristics were similar between the groups. No evidence of differences in CK release (p=0.92), troponin T (p=0.85) or CMR-assessed infarct size (p=0.254) were evident. In contrast there was a reduction in myocardial salvage index (p=0.05) and MACE at 1 year (2.6% vs 15.8%, p=0.04) in the nitrite group. In a 66-patient sub-group with TIMI≤1 flow there was reduced serum CK (p=0.030) and a 19% reduction in CMR-determined infarct size (p=0.034) with nitrite. No adverse effects of nitrite were detected.Conclusions: In this phase II study intra-coronary nitrite infusion did not alter infarct size although a trend to improved myocardial salvage index and a significant reduction in MACE was evident. In a sub-group of patients with TIMI flow≤1 nitrite reduced infarct size and MACE and improved myocardial salvage index indicating that a phase III clinical trial assessing intra-coronary nitrite administration as an adjunct to PCI in STEMI patients is warranted. Clinical Trial Registration: http://clinicaltrials.gov - NCT01584453.

U2 - 10.1161/CIRCRESAHA.116.305082

DO - 10.1161/CIRCRESAHA.116.305082

M3 - Article

C2 - 25512434

SN - 0009-7330

VL - 116

SP - 437

EP - 447

JO - Circulation Research

JF - Circulation Research

IS - 3

ER -