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Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.
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.
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.
PMID: 10475182 [PubMed - indexed for MEDLINE]