Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial

Background Bolus fibrinolytic therapy facilitates early efficient instituti on of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind , randomised, controlled trial to assess the efficacy and safety of tenecte plase compared with alteplase. Methods In 1021 hospitals, we randomly assigned 16 949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (less than or equal to 100 mg) or single-bolus injection of tenecteplase ( 30-50 mg according to bodyweight). All patients received aspirin and hepari n (target activated partial thromboplastin time 50-75 s). The primary outco me was equivalence in all-cause mortality at 30 days. Findings Covariate-adjusted 30-day mortality rates were almost identical fo r the two groups-6.18% for tenecteplase and 6.15% for alteplase. The 95% on e-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day m ortality, whichever difference proved smaller). Rates of intracranial haemo rrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but f ewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and le ss need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tene cteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with t enecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13] ). Interpretation Tenecteplase and alteplase were equivalent for 30-day mortal ity. The ease of administration of tenecteplase may facilitate more rapid t reatment in and out of hospital.