Effects of Intracoronary Pro-urokinase or Tirofiban on Coronary Flow During Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Multi-Center, Placebo-Controlled, Single-Blind, Randomized Clinical Trial

Abstract

Background: To determine whether intracoronary pro-urokinase or tirofiban improves myocardial reperfusion during primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).Methods: The study included patients with acute STEMI presenting within 12 h of symptoms at 11 hospitals in China between November 2015 and July 2017. Patients were randomized to receive selective intracoronary infusion of recombinant pro-urokinase (20 mg), tirofiban (10 μg/kg), or saline (20 mL) proximal to the infarct-related lesion over a 3-min period before stent implantation during primary PCI. The primary outcome was final corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) after PCI.Results: This study included 345 patients. Initial angiography identified a high-grade thrombus (TIMI 4–5) in 80% of patients. Final CTFC after PCI was significantly lower in the pro-urokinase (P < 0.001) and tirofiban (P < 0.001) groups than in the saline group and similar between the pro-urokinase and tirofiban groups (P > 0.05). The pro-urokinase (P = 0.008) and tirofiban groups (P = 0.022) had more complete ST-segment resolution at 2 h and lower peak creatine kinase-MB levels after PCI than the saline group (P = 0.006 and P = 0.023). The 30-day incidence of major adverse cardiac events was 4.5% in the pro-urokinase group, 3.4% in the tirofiban group, and 2.6% in the saline group. The incidence of in-hospital TIMI major bleeding events was low and comparable between groups.Conclusions: Adjunctive intracoronary pro-urokinase or tirofiban given before stent implantation during primary PCI improves myocardial reperfusion without increasing the incidence of major bleeding events.

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project

“…In support of these pathological mechanisms, a recent randomized controlled trial showed that even under the current intensive treatment measures (60.8% ticagrelor and 50.7% thrombus aspiration), GPI use in STEMI patients with high thrombus burden is capable of improving myocardial perfusion, as shown by lower TIMI frame counts. 19 However, this study was underpowered to detect differences in bleeding and mortality risk.…”

Impact of intracoronary reteplase during primary percutaneous coronary intervention on infarct size in large anterior myocardial infarction: rationale and design of the RECOVER II trial

“…The pro-UK dose (20 mg) utilized for intracoronary infusion in the ERUPTION trial approximated two-fifths of the common entire dose administered intravenously in fibrinolytic treatment of myocardial infarction, which could ameliorate myocardial reperfusion and decrease infarct size with no additional major bleeding events (7). Streptokinase dose (250 kU) in Sezer et al was 25% of the total dose usually given intravenously due to elevated bleeding risk (5).…”

“…However, PCI supplemented with adjunctive intravenous fibrinolytic treatment provided before PCI induces paradoxical thrombin activation, clotting and bleeding. Since Sezer and collaborators reported that the modified approach applying intracoronary low-dose thrombolytic treatment with streptokinase at 250 kU upon primary PCI could ameliorate myocardial reperfusion and reduce infarct size, the possible effectiveness of combined intracoronary fibrinolytic treatment in primary PCI attracts increasing attention (5)(6)(7)(8). Our recently published ERUPTION trial also showed that adjunctive intracoronary pro-urokinase (pro-UK) administered prior to stent implantation during primary PCI could ameliorate myocardial reperfusion and reduce infarct size estimated from creatine kinase with no additional major bleeding events (7).…”

“…Since Sezer and collaborators reported that the modified approach applying intracoronary low-dose thrombolytic treatment with streptokinase at 250 kU upon primary PCI could ameliorate myocardial reperfusion and reduce infarct size, the possible effectiveness of combined intracoronary fibrinolytic treatment in primary PCI attracts increasing attention (5)(6)(7)(8). Our recently published ERUPTION trial also showed that adjunctive intracoronary pro-urokinase (pro-UK) administered prior to stent implantation during primary PCI could ameliorate myocardial reperfusion and reduce infarct size estimated from creatine kinase with no additional major bleeding events (7). However, the T-TIME study found no benefit of low intracoronary alteplase dose in decreasing microvascular obstruction (MVO) and infarct size determined by contrast-enhanced cardiac magnetic resonance imaging (CMR) in acute STEMI cases who presented within 6 h of symptom onset (8).…”

Intracoronary artery retrograde thrombolysis combined with percutaneous coronary interventions for ST-segment elevation myocardial infarction complicated with diabetes mellitus: A case report and literature review

“…PPCI has been shown to have great advantages in establishing effective and early recanalization of infarct-related arteries, reducing major adverse cardiovascular events (MACE), and improving survival (14)(15)(16). However, intracoronary thrombus remains the bane of interventional cardiologists (17,18). Failure to recanalize, suboptimal outcomes, distal embolization, noreflow, and impaired myocardial perfusion are some of the unresolved difficulties that frequently arise during PCI in patients with a high intracoronary thrombus burden, indicating an unmet need (19,20).…”