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 (≥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% Cl 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.
