BACKGROUND AND OBJECTIVES: The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight.

METHODS: We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (=1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process.

RESULTS: Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; p = 0.012; I2 = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; p = 0.008; I2 = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; p = 0.034; I2 = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; p = 0.142; I2 = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; p = 0.456; I2 = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; p = 0.727; I2 = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; p = 0.044; I2 = 0%).

DISCUSSION: The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

Emergency Medicine rater

This was a large meta-analysis of trials comparing tPA with TNK showing very mild benefits for TNK. This evidence supports the ongoing transition from tPA to TNK in clinical practice.

Internal Medicine rater

In stroke, time is clearly key. The faster you can safely get a vessel open, the better someone will do. This systematic review of 11 studies compared tPA with TNK, a 3rd generation fibrinolytic. The pooled sample size was large enough to see a difference in both functional outcome in disability without a difference in bleeding. My hospital has switched to using this as its fibrinolytic of choice.

Neurology rater

This metanalysis that was updated with the inclusion of the latest trials, confirms the non-inferiority and also the superiority of tenecteplase compared with alteplase in terms of outcome and is easy to handle and equally safe. Hopefully, tenecteplase will gradually be the first-choice thrombolytic drug and we will be as confident with it as we are now with alteplase.

Neurology rater

I will look at changing our hospital guidelines based on this article.