Tenecteplase is a
fibrinolytic drug with higher
fibrin specificity and longer half-life than the standard
stroke thrombolytic,
alteplase, permitting the convenience of single bolus administration.
Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat
ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic
hemorrhages. Investigated as a thrombolytic for
ischemic stroke over the past 15 years,
tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published
stroke clinical trials of
tenecteplase that (1) performed randomized comparisons with
alteplase, (2) compared different doses of
tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with
alteplase. These and other phase 2 studies compared different
tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic
intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of
tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to
tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic
intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for
stroke include intravenous
tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to
alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of
tenecteplase and
alteplase for
stroke thrombolysis and answer questions of
tenecteplase efficacy in the >4.5-hour time window, in
wake-up stroke, and in combination with endovascular
thrombectomy.