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

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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).

Methods and results

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. control. 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.

Clinical Trial registration Identifier: NCT01747174;

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