Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Tenecteplase vs Alteplase Before Endovascular Therapy in Basilar Artery Occlusion.

OBJECTIVE: To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO). METHODS: To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated. RESULTS: We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7-32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3-12; p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40-71] minutes) vs alteplase-treated patients (110 [IQR 51-185] minutes; p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; p = 0.9). CONCLUSIONS: TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted. CLINICALTRIALSGOV IDENTIFIERS: NCT02388061 and NCT03340493. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO.

Tenecteplase for thrombolysis in stroke patients: Systematic review with meta-analysis.

INTRODUCTION: Alteplase is an approved treatment for acute ischemic stroke. Tenecteplase is a genetically modified form of alteplase, with lower cost and a more favourable pharmacokinetic profile allowing bolus injection. The aim of this study was to compare both drugs in adult patients with acute ischemic stroke undergoing thrombolysis. MATERIAL AND METHODS: PubMed and CENTRAL were searched for observational and experimental studies comparing both drugs in the population of interest. Additional studies were sought in clinical trial registries and by means of reference check. The efficacy outcomes of interest were functional status at 3 months, recanalization and early neurological improvement (ENI). The safety outcomes of interest were cerebral haemorrhage (ICH), symptomatic ICH and mortality. The effect measure of interest was the absolute risk difference (ARD). Effect measures for each outcome were pooled across studies using random effect models. RESULTS: Eight studies were included, involving 2031 patients. Overall, there were no differences in terms of good or excellent functional outcome (ARR = 0.07 and 0.03 respectively, p > 0.05 for both comparisons) but tenecteplase patients showed higher rates of recanalization (ARD = 0.11, 95% CI [0.01;0.20]) and ENI (ARD = 0.10, 95% CI [0.02;0.17]). There were no differences between groups in terms of ICH (ARD = -0.02, 95% CI [-0.06;0.01]), symptomatic ICH (ARD = 0.00, 95% CI [-0.01;0.02]) or death (ARD = 0.00, 95% CI [-0.03;0.03]). CONCLUSION: Tenecteplase is an alternative to alteplase for stroke thrombolysis, with lower cost and a more favourable pharmacokinetic profile.