title: Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.
abstract: 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.
  
  
  RESULTS
  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]).
  
  
  CONCLUSIONS
  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.
authors.forename: F
authors.initials: F
authors.lastname: Van De Werf
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authors.lastname: Adgey
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authors.initials: D
authors.lastname: Ardissino
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authors.lastname: Armstrong
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authors.lastname: Aylward
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authors.lastname: Barbash
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authors.lastname: Betriu
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authors.lastname: Binbrek
authors.forename: R
authors.initials: R
authors.lastname: Califf
authors.forename: R
authors.initials: R
authors.lastname: Diaz
authors.forename: R
authors.initials: R
authors.lastname: Fanebust
authors.forename: K
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authors.lastname: Fox
authors.forename: C
authors.initials: C
authors.lastname: Granger
authors.forename: J
authors.initials: J
authors.lastname: Heikkilä
authors.forename: S
authors.initials: S
authors.lastname: Husted
authors.forename: P
authors.initials: P
authors.lastname: Jansky
authors.forename: A
authors.initials: A
authors.lastname: Langer
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authors.lastname: Lupi
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authors.initials: A
authors.lastname: Maseri
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: J
authors.initials: J
authors.lastname: Mlczoch
authors.forename: D
authors.initials: D
authors.lastname: Mocceti
authors.forename: D
authors.initials: D
authors.lastname: Myburgh
authors.forename: A
authors.initials: A
authors.lastname: Oto
authors.forename: E
authors.initials: E
authors.lastname: Paolasso
authors.forename: K
authors.initials: K
authors.lastname: Pehrsson
authors.forename: R
authors.initials: R
authors.lastname: Seabra-Gomes
authors.forename: L
authors.initials: L
authors.lastname: Soares-Piegas
authors.forename: D
authors.initials: D
authors.lastname: Sùgrue
authors.forename: M
authors.initials: M
authors.lastname: Tendera
authors.forename: E
authors.initials: E
authors.lastname: Topol
authors.forename: P
authors.initials: P
authors.lastname: Toutouzas
authors.forename: A
authors.initials: A
authors.lastname: Vahanian
authors.forename: F
authors.initials: F
authors.lastname: Verheugt
authors.forename: L
authors.initials: L
authors.lastname: Wallentin
authors.forename: H
authors.initials: H
authors.lastname: White
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase