Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.
(Clinical Trial;Journal Article;Multicenter Study)
BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution 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 tenecteplase 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 (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-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 mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.
Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators, ; Van De Werf, F; Adgey, J; Ardissino, D; Armstrong, PW; Aylward, P; Barbash, G; Betriu, A; Binbrek, AS; Califf, R; Diaz, R; Fanebust, R; Fox, K; Granger, C; Heikkilä, J; Husted, S; Jansky, P; Langer, A; Lupi, E; Maseri, A; Meyer, J; Mlczoch, J; Mocceti, D; Myburgh, D; Oto, A; Paolasso, E; Pehrsson, K; Seabra-Gomes, R; Soares-Piegas, L; Sùgrue, D; Tendera, M; Topol, E; Toutouzas, P; Vahanian, A; Verheugt, F; Wallentin, L; White, H
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