Alteplase vs. Tenecteplase: How Does Symptomatic Intracranial Hemorrhage Occur?

*Only for medical professionals to read and refer to the ISC conference essence content express! For patients with acute ischemic stroke (AIS), recanalization, or reperfusion therapy, is the most important part of neurological recovery
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The thrombolytic drug alteplase has been widely used, and tenecteplase has attracted more and more attention of neurologists due to its potential value and usage advantages
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Previous studies have demonstrated pharmacological and clinical utility advantages for tenecteplase compared to alteplase, but no differences were observed in the percentage of symptomatic intracranial hemorrhage (sICH) in actual randomized trials, which may require Larger clinical trials to explore further
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At the 2022 International Stroke Congress (ISC), members of the team of Prof.
Steven Warach from The University of Texas at Austin presented their study[1]—in acute stroke treatment, after routine tenecteplase and alteplase intravenous thrombolysis, the incidence of sICH
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How about Steven Warach MD, PhD, FAHAUniversity of Texas at Austin? The researchers used data from the CERTAIN study (3 different countries, 25 regions, 3-year registry data from more than 100 hospitals) to compare the incidence of sICH during intravenous thrombolysis with 2 drugs.
Compared with previous studies, the sample size Very large, with 7891 patients included in the primary analysis
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We defined sICH as clinical worsening of an NIHSS score of at least 4 and attributed to parenchymal hematoma, subarachnoid hemorrhage, or intraventricular hemorrhage
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Logistic regression was used for binary variables, adjusting for differences in sICH definitions for age, baseline NIHSS, thrombectomy, and source hospital network, and the Mann-Whitney test for continuous baseline variables
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The above table shows the sample characteristics.
It can be found that the tenecteplase group is relatively older, has a higher proportion of males, has a higher NIHSS score, and has a higher proportion of mechanical thrombectomy
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The results of the analysis showed that the incidence of sICH was 3.
71% and 2.
13% in patients receiving alteplase and tenecteplase, respectively: adjusted OR (95% CI) = 0.
49 (0.
31-0.
76), p = 0.
002
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In addition, for patients who did not undergo thrombectomy after thrombolysis, the incidence of sICH in the alteplase group and tenecteplase group was 3.
00% and 1.
74%, respectively, adjusted OR (95% CI) = 0.
48 (0.
27-0.
87 ), p=0.
016
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It is worth mentioning that for patients treated with thrombectomy, the incidence of sICH in the alteplase group and tenecteplase group was 6.
80% and 2.
80%, respectively, with an adjusted OR (95% CI) of 0.
60 (0.
31-1.
16).
), p=0.
129
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In conclusion, in a preliminary analysis of a large multicenter registry, tenecteplase was associated with a lower incidence of sICH compared with alteplase in ischemic stroke
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Wonderful Review At last year's ISC Congress, Professor Jeffrey Saver, Professor Patrick Lyden, Professor Shelagh Coutts and Professor Steven Warach had a debate on whether tenecteplase was ready for clinical practice
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Prof.
Jeffrey Saver from Zhengfang listed 9 criteria for the application of new drugs in routine clinical practice.
If a new drug meets 5-7 criteria, it has the possibility of clinical application
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At the same time, he believes that tenecteplase meets these nine criteria
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(1) The pharmacological mechanism is clear: tenecteplase is modified from alteplase, which has many physiological advantages such as longer half-life and higher specificity to fibrin
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(2) Conclusive evidence from preclinical studies: Tenecteplase in vitro and animal tests have shown clear evidence of thrombolysis
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(3) Demonstrated benefit and safety in clinical studies of similar conditions: A meta-analysis of myocardial infarction thrombolysis trials showed that compared with alteplase, tenecteplase has a good safety profile
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(4) Advantages of clinical practice: Tenecteplase is more convenient to use because it can be injected within 1 minute, especially in the era of new coronary pneumonia
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(5) RCT studies show effectiveness: a meta-analysis published by Professor Jeffrey Saver in 2019 [2] showed that tenecteplase was not inferior to alteplase in the treatment of AIS
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(6) Guideline recognition: Tenecteplase is recommended in many national guidelines
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(7) Support from drug regulatory authorities: The U.
S.
Food and Drug Administration (FDA) approved a revised plan for thrombolysis trials in 2021, and the use of tenecteplase is also one of the standard treatments for thrombolysis
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(8) Real-world diagnosis and treatment practice shows effectiveness
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(9) Clinician support
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In addition, Professor Steven Warach said that he and Professor Jeffrey Saver published in JAMA Neurology tenecteplase for stroke thrombolytic therapy can reduce the spread of emergency new crowns and alleviate the shortage of alteplase [3], summed up in detail the replacement The advantages of neplase include: (1) shorter preparation time; (2) shorter injection time; (3) no need to open and maintain a second venous access; (4) no need for an IV pump; ( 5) The time required for patient transfer after intravenous administration is shorter
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On the contrary, Professor Patrick Lyden and Professor Shelagh Coutts believe that although there are advantages in some clinical trials, more data are still needed to confirm
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Professor Patrick Lyden emphasized at the time that not only the outcome of reperfusion rate should be concerned, but also the improvement of neurological function in patients at 90 days
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Professor Patrick Lyden summarized the published tenecteplase thrombolytic therapy studies and ongoing studies at the time.
From the study of Parsons et al.
in 2012 to the ATTEST study and the EXTEND-IA trial in 2018, there are many interesting We are pleased with the results, but it should also be noted that most trials have small numbers of patients [4]
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In addition, some trials included a proportion of transient ischemic attack (TIA) patients and stroke mimic patients (pseudo-stroke), and Professor Patrick Lyden finally said: "Don't think we already know the answer, It's a test that is as rigorous as a machine running to get data
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" "I don't care about receiving alteplase treatment or receiving tenecteplase treatment, the important thing is to effectively improve symptoms
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"At this year's ISC Congress, the topic of debate was no longer tenecteplase, but "late window thrombolysis is applicable to all patients who are eligible by DWI-FLAIR mismatch or perfusion mismatch.
" Alteplase or Tenecteplase? Or according to the guide? "Should all eligible patients undergo intravenous thrombolysis prior to thrombectomy?" Or is intravenous thrombolysis only performed when thrombectomy is not immediately available in the field? ".
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The follow-up "Medical Neurology Channel" will continue to record the hot content of the ISC conference, so stay tuned! Reference source: [1] Warach SJ, Ranta A, Song SS, et al.
Comparative Effectiveness Of Routine Tenecteplase Thrombolysis In Acute Stroke Compared With Alteplase:An INternational Collaboration(CERTAIN Collaboration):Rates Of Symptomatic Intracranial Hemorrhage[J].
Stroke,2022,53(Suppl_1):A43-A43.
[2]Burgos AM,Saver JL.
Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke:Meta-Analysis of 5 Randomized Trials.
Stroke.
2019;50(8):2156-2162.
[3]Warach SJ,Saver JL.
Stroke Thrombolysis With Tenecteplase to Reduce Department Emergency Spread of Coronavirus Disease 2019 and Shortages of Alteplase [published online ahead of print, 2020 Jul 20].
JAMA Neurol.
2020; 10.