Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time

BACKGROUND Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. OBJECTIVES This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary atteptase infused early after coronary reperfusion associates with ischemic time. METHODS This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; >= 2 h but <4 h, n 235;>= 4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Partidpants were randomly assigned to treatment with placebo (n = 151), atteptase 10 mg (n = 144), or atteptase 20 mg (n 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). RESULTS Overall, there was no assodation between atteptase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time >= 4 to 6 h, atteptase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 311% (10 mg) versus 5.20% (20 mg); p 0.009 for the trend. The interaction between ischemic time and atteptase dose was statistically significant (p = 0.018). CONCLUSION In patients presenting with ST-segment elevation myocardial infarction and an ischemic time >= 4 to 6 h, adjunctive treatment with low-dose intracoronary atteptase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary atteptase may be harmful for this subgroup. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.