McCartney PJ, et al. - In patients undergoing primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction (STEMI), researchers investigated if using low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion would attenuate microvascular obstruction. Findings revealed no reduction in microvascular obstruction with adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention among patients with acute STEMI presenting within 6 hours of symptoms, and therefore, this treatment strategy was not supported in this study.

Methods

• This study included 440 patients presenting at 11 hospitals in the UK within 6 hours of STEMI due to a proximal–mid-vessel occlusion of a major coronary artery.
• These subjects were randomized in a 1:1:1 dose-ranging trial design between March 17, 2016 and December 21, 2017.
• Patients were followed-up to 3 months, ending on April 12, 2018.
• Participants were randomly treated with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145) by manual infusion over 5 to 10 minutes.
• They carried out the intervention at different time points: early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery, and before stent implant.
• The amount of microvascular obstruction (% left ventricular mass) was assessed as primary outcome, using contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment.
• The alteplase 20-mg group and the placebo group were compared primarily; if not significant, the alteplase 10-mg group vs the placebo group was considered a secondary analysis.

Results

• Since conditional power for the primary outcome based on a prespecified analysis of the first 267 randomized participants was less than 30% in both treatment groups (futility criterion), recruitment was ended on December 21, 2017.
• A total of 440 patients were randomized, with mean age 60.5 years, 15% being women.
• Among these subjects, 396 patients (90%) achieved the primary end point, 17 (3.9%) withdrew, and all others were followed up to 3 months.
• The findings of the primary analysis revealed no difference in the mean microvascular obstruction between the 20-mg alteplase and placebo groups (3.5% vs 2.3%; estimated difference, 1.16%; 95% CI, −0.08% to 2.41%; P = .32) nor in the analysis of 10-mg alteplase vs placebo groups (2.6% vs 2.3%; estimated difference, 0.29%; 95% CI, −0.76% to 1.35%; P = .74).
• In 15 patients (10.1%) in the placebo group, 18 (12.9%) in the 10-mg alteplase group, and 12 (8.2%) in the 20-mg alteplase group, the occurrence of major adverse cardiac events (cardiac death, nonfatal MI, unplanned hospitalization for heart failure) was seen.