Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial

• Published in: European heart journal Vol. 37; no. 24; pp. 1910 - 1919
• Main Authors: Nazir, Sheraz A, McCann, Gerry P, Greenwood, John P, Kunadian, Vijay, Khan, Jamal N, Mahmoud, Islam Z, Blackman, Daniel J, Been, Martin, Abrams, Keith R, Shipley, Lorraine, Wilcox, Robert, Adgey, A A Jennifer, Gershlick, Anthony H
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 21-06-2016
• Subjects: Clinical Research; Editor's Choice; Humans; Magnetic Resonance Imaging; Percutaneous Coronary Intervention; Prospective Studies; ST Elevation Myocardial Infarction; Thrombectomy; Treatment Outcome; Microvascular obstruction; Nitroprusside; Adenosine; Ischaemia-reperfusion injury; Acute myocardial infarction; Magnetic resonance Imaging
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehw136

Microvascular obstruction (MVO) following primary percutaneous coronary intervention (PPCI) treatment of ST-segment elevation myocardial infarction (STEMI) contributes to infarct expansion, left ventricular (LV) remodelling, and worse clinical outcomes. The REFLO-STEMI trial tested whether intra-coronary (IC) high-dose adenosine or sodium nitroprusside (SNP) reduce infarct size and/or MVO determined by cardiac magnetic resonance (CMR).
REFLO-STEMI, a prospective, open-label, multi-centre trial with blinded endpoints, randomized (1:1:1) 247 STEMI patients with single vessel disease presenting within 6 h of symptom onset to IC adenosine (2-3 mg total) or SNP (500 μg total) immediately following thrombectomy and again following stenting, or to standard PPCI. The primary endpoint was infarct size % LV mass (%LVM) on CMR undertaken 24-96 h after PPCI (n = 197). Clinical follow-up was to 6 months. There was no significant difference in infarct size (%LVM, median, interquartile range, IQR) between adenosine (10.1, 4.7-16.2), SNP (10.0, 4.2-15.8), and control (8.3, 1.9-14.0), P = 0.062 and P = 0.160, respectively, vs.
MVO (% LVM, median, IQR) was similar across groups (1.0, 0.0-3.7, P = 0.205 and 0.6, 0.0-2.4, P = 0.244 for adenosine and SNP, respectively, vs. control 0.3, 0.0-2.8). On per-protocol analysis, infarct size (%LV mass, 12.0 vs. 8.3, P = 0.031), major adverse cardiac events (hazard ratio, HR, 5.39 [1.18-24.60], P = 0.04) at 30 days and 6 months (HR 6.53 [1.46-29.2], P = 0.01) were increased and ejection fraction reduced (42.5 ± 7.2% vs. 45.7 ± 8.0%, P = 0.027) in adenosine-treated patients compared with control.
High-dose IC adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR. Furthermore, adenosine may adversely affect mid-term clinical outcome.
ClinicalTrials.gov Identifier: NCT01747174; https://clinicaltrials.gov/ct2/show/NCT01747174.