Acute ischemic stroke (AIS) patients who present within the window for treatment are typically treated with Alteplase. Additionally, cardiac arrest caused by suspected pulmonary embolism (PE) and myocardial infarction (MI) can all be treated with Alteplase. Tenecteplase comes with a proven indication in MI, looking to expand its use to ischemic stroke, whereas Alteplase made a name for itself in the brain and heart.
Tenecteplase should be seriously considered as an alternative to Alteplase due to its superior pharmacokinetic and pharmacodynamic profile when compared to Alteplase. Tenecteplase is more effective than Alteplase in terms of a number of significant outcomes. Even for nonsignificant outcomes, Tenecteplase administration has a tendency to be beneficial. Read the article to know more.
What Are the Benefits of Tenecteplase?
Tenecteplase has theoretical advantages over Alteplase because it has a longer half-life and a higher level of fibrin specificity. In contrast to Alteplase, which requires a bolus followed by a one-hour infusion, this enables the administration of a single dose over five to ten seconds. Tenecteplase has extensive data for this off-label use and is currently approved by the Food and Drug Administration (FDA) for the treatment of ST-segment elevated myocardial infarction. Tenecteplase has also been studied in the treatment of acute ischemic stroke. The TNK-S2B, Australian TNK, ATTEST, Nor test, and TNK-S2 are the trials that have evaluated the use of Tenecteplase in acute ischemic stroke. Following its greater rate of early neurological recovery and non-inferiority in terms of safety results, TNK in the dose of 0.25 milligrams is a favorable alternative to Alteplase as the standard of care in patients with AIS (acute ischemic stroke) who present within 4.5 hours of symptom onset. However, evidence for TNK's potential in AIS presenting after 4.5 hours, wake-up stroke, and minor stroke or TIA (transient ischemic attack) is still lacking, necessitating the conduct of additional double-blind, large-scale, and pragmatic RCTs.
What Are the Safety Concerns for Using Tenecteplase?
It is safe and effective to use Tenecteplase, a modified recombinant tissue plasminogen activator, to treat acute ischemic stroke. The only thrombolytic medication with FDA approval for thrombolysis in AIS is Alteplase. When administered within the four to five window, Alteplase can result in a 28 percent reduction in disability at 90 days and quick symptom improvement. Implementation of Alteplase is limited despite its potential for a recovery devoid of disability because of the limited time window and unfavorable side effects, such as a six percent chance of symptomatic hemorrhage. Additionally, Alteplase has only mild fibrinolytic efficacy, with less than 50 percent of patients experiencing arterial recanalization. Only 50 percent of patients who achieve recanalization do so within two hours of drug administration. Alteplase’s adverse effects on the ischemic brain, including cytotoxicity and increased permeability of the blood-brain barrier, have also been a growing source of worry.
In this situation, the acceptance of thrombolytic therapy for stroke can be increased by developing thrombolytic medicines that are secure, simple to use, and efficient. Following reports from the ASSENT 2 trial, the FDA has approved Tenecteplase (TNK), a genetically altered form of Alteplase, for thrombolysis in acute myocardial infarction. TNK induces coronary reperfusion more quickly than Alteplase while having comparable mortality rates, according to numerous clinical traits comparing the two drugs in acute MI. The success of treatments for acute MI and animal models of the disease has sparked interest in substituting Alteplase for TNK therapy in AIS. TNK is an appealing substitute due to a number of benefits, including its generally low cost, high fibrin specialty, prolonged plasma half-life, and improved plasminogen activator inhibitor.
Three molecular substitutions separate Tenecteplase from Alteplase, altering the drug’s pharmacokinetic and pharmacodynamic characteristics. These modifications led to an increase in the half-life of Alteplase and Tenecteplase from four minutes to 20 and 24 minutes, respectively. Tenecteplase’s long half life allows for single bolus administration rather than one hour-long infusion, which prolongs the time the drug is exposed to the clot. A higher affinity to fibrin-rich clots and platelet-rich thrombi, as well as greater thrombolytic potency when compared to Alteplase, are both made possible by changes in the molecular structure. And finally, it has been discovered that Tenecteplase consumes less fibrinogen, plasminogen, and alpha-two antiplasmins, which lowers the risk of bleeding.
What Are the Results of the Study of Tenecteplase Over Alteplase?
It is FDA approved indication based on studies that finished between 1997 and 1999. Tenecteplase 0.5 mg per kg and Alteplase 1.1 mg per kg were compared in a randomized, double-blind fashion (blinds both the subjects and the researchers to the treatment allocation) in patients with acute MI by researchers in the historic trial ASSENT-2. However, the rates of mortality and symptomatic intracerebral hemorrhage were similar in both groups. The Tenecteplase group had lower rates of cerebral bleeding and blood transfusions.
The first Tenecteplase for the AIS study was released about six years after the release of ASSENT-2. Tenecteplase 0.1 to 0.4 mg per kg was found to be safe for treating acute ischemic stroke in a dose escalation study. Five years after the completion of this study, the first randomized phase 2 trial comparing Tenecteplase at doses of 0.1, 0.25, and 0.4 mg per kg to Alteplase at the recommended dose was published. While the slow enrollment in this phase-2 trial led to early termination, preliminary findings that showed increased frequency in symptomatic intracerebral hemorrhage in the Tenecteplase of 0.4 mg per kg group were still published.
What Are the Contraindications of Tenecteplase?
The contraindications include:
Cerebrovascular accident history.
Active internal bleeding.
Within two months of intracranial or intraspinal surgery or trauma.
Tenecteplase, which shares a similar safety profile with Alteplase, is associated with higher rates of both excellent functional outcomes and early neurological improvement when administered at a dose of 0.25 mg per kilogram. Tenecteplase may be a good substitute for Alteplase due to its superior pharmacokinetics. A direct comparison of Tenecteplase with thrombectomy and the effect of NIHSS (National Institute of Health Stroke Scale) scores on the efficacy and safety profiles of Tenecteplase is just a couple of the unanswered questions that require further research.