Abbas Aslam
CAT:
Clinical Scenario: 62-year-old male, presented to the emergency department after experiencing sudden onset of right-sided weakness, slurred speech, and facial droop, which started 1.5 hours ago while watching television. His wife, who was with him, noted the symptoms began suddenly, and they immediately called emergency services
Search Question: In adults with acute ischemic stroke, does the administration of Tenecteplase compared to Alteplase result in better functional neurological outcomes, lower rates of symptomatic intracerebral hemorrhage, and reduced mortality?
Question Type: What kind of question is this? (boxes now checkable in Word)
☐Prevalence ☐Screening ☐Diagnosis
☐Prognosis ☒Treatment ☐Harms
Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)?
Please explain your choices.
| P | I | C | O |
| Acute ischemic stroke | Tenecteplase | Alteplase | Functional outcomes |
| Stroke | TNK | tPA | Neurological outcomes |
| Tissue plasminogen activator | Symptomatic intracerebral hemorrhage | ||
Pubmed
Acute Ischemic Stroke AND Tenecteplase AND Alteplase AND Neurological outcomes years→45
Filters: Free Full text, Meta-Analysis, Systemic Review, RCT, last 10 years→ Since 2014→15
Cochrane
Acute Ischemic Stroke AND Tenecteplase AND Alteplase AND Functional outcomes→25
Filters: Since 2014→5
Science Direct
Stroke AND Tenecteplase AND Alteplase AND Symptomatic Cerebral Hemorrhage→5
Since 2014→5
After filtering out which articles were acceptable to be used as evidence, I was able to read abstracts from articles provided to see whether they pertain exactly to my topic before making my final decision.
Article 1:
| Citation:Potla N, Ganti L. Tenecteplase vs. alteplase for acute ischemic stroke: a systematic review. Int J Emerg Med. 2022 Jan 4;15(1):1. doi: 10.1186/s12245-021-00399-w. PMID: 34983359; PMCID: PMC8903524. |
| Type of article: A systematic review |
| Abstract:Background:Thrombolysis for acute ischemic stroke (AIS) with alteplase is the currently approved therapy for patients who present within 4.5 h of symptom onset and meet criteria. Recently, there has been interest in the thrombolytic tenecteplase, a modified version of alteplase, due to its lower cost, ease of administration, and studies reporting better outcomes when compared to alteplase. This systematic review compares the efficacy of tenecteplase vs. alteplase with regard to three outcomes: (1) rate of symptomatic hemorrhage, (2) functional outcome at 90 days, and (3) reperfusion grade after thrombectomy to compare the efficacy of both thrombolytics in AIS METHODS: The search was conducted in August 2021 in PubMed, filtered for randomized controlled trials, and studies in English. The main search term was “tenecteplase for acute stroke.”Materials and Methods:The search was conducted in August 2021 in PubMed, filtered for randomized controlled trials, and studies in English. The main search term was “tenecteplase for acute stroke.”Results:A total of 6 randomized clinical trials including 1675 patients with AIS was included. No one’s study compared alteplase to tenecteplase with all three outcomes after acute ischemic stroke; however, by using a combination of the results, this systematic review summarizes whether tenecteplase outperforms alteplase.Conclusion: The available evidence suggests that tenecteplase appears to be a better thrombolytic agent for acute ischemic stroke when compared to alteplase. |
| Why I chose it: This article is a great choice for my PICO question because it directly compares Tenecteplase and Alteplase in adults with acute ischemic stroke, focusing on the outcomes I’m interested in: functional neurological recovery, rates of symptomatic intracerebral hemorrhage, and mortality. With 1675 patients included, 782 treated with Tenecteplase and 727 with Alteplase, it provides a solid comparison. The functional outcomes are measured using the modified Rankin Scale (mRS), showing that Tenecteplase is either as effective or better in terms of recovery. It also looks at symptomatic intracranial hemorrhage rates, showing Tenecteplase has either similar or lower risks, especially at certain doses. Plus, the article discusses how Tenecteplase improves reperfusion rates after thrombectomy and is easier to administer, which aligns well with my PICO focus. |
Article 2
| Citation:Shen Z, Bao N, Tang M, Yang Y, Li J, Liu W, Jiang G. Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. Neurol Ther. 2023 Oct;12(5):1553-1572. doi: 10.1007/s40120-023-00530-4. Epub 2023 Aug 8. PMID: 37552459; PMCID: PMC10444744. |
| Type of article: A systematic review and meta analysis |
| AbstractBackground:In recent years, as one of the drugs for the treatment of acute ischemic stroke (AIS), the clinical application of tenecteplase is still controversial. Therefore, we aimed to evaluate the safety and efficacy of tenecteplase versus alteplase to guide clinical practice.Materials and Methods: A search of PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023 was conducted to identify eligible articles. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 and Stata 17 were used to perform the meta-analysis and detect publication bias, and risk ratios (RRs) with 95% confidence intervals (95% CIs) were reported for each outcome measure.Results: A total of 1326 records were retrieved in this meta-analysis. As a result of the limited reports on tenecteplase in patients with AIS and the lack of high-quality randomized controlled trials (RCTs), and considering the impact of publication bias, we did not include any of these studies published before 2015. Ultimately we included 16 RCTs with a total of 7508 patients, including 3940 patients treated with alteplase and 3568 patients treated with tenecteplase. Tenecteplase was associated with better early neurological improvement (RR 0.10; 95% CI 0.00-0.19; P = 0.04), recanalization of blood vessels (RR 0.24; 95% CI 0.07-0.40; P = 0.01), and 90-day excellent neurological recovery (RR 0.12; 95% CI 0.01-0.24; P = 0.04). In addition, there were no significant differences in other efficacy and safety outcomes between the two groups. The funnel plot and Begg’s as well as Egger’s tests showed no significant publication bias.Conclusion:This meta-analysis showed that tenecteplase was not inferior to alteplase in early thrombolytic therapy in patients with AIS, and was even better than alteplase on some efficacy outcomes with no significant differences in safety. However, as a result of some inherent limitations of this study, more high-quality prospective clinical studies are needed to confirm these results. |
| Why I chose it: This article is a strong choice for my PICO question because it directly compares tenecteplase and alteplase in patients with acute ischemic stroke, which aligns perfectly with my focus. The meta-analysis includes a substantial patient population from multiple studies, providing robust data on key outcomes like functional neurological recovery, rates of symptomatic intracerebral hemorrhage (sICH), and mortality. Additionally, it highlights both the efficacy and safety of tenecteplase compared to alteplase, which is critical for addressing all aspects of my question. The pharmacokinetic benefits of tenecteplase discussed in the article also provide valuable insights into why it might offer advantages over alteplase, supporting the relevance of this study to my research. |
Article 3
| Citation:Ma P, Zhang Y, Chang L, Li X, Diao Y, Chang H, Hui L. Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis. J Neurol. 2022 Oct;269(10):5262-5271. doi: 10.1007/s00415-022-11242-4. Epub 2022 Jul 1. PMID: 35776193. |
| Type of article: A systematic review and meta analysis |
| AbstractBackground:At present, studies regarding the efficacy and safety of tenecteplase for the treatment of patients with acute ischemic stroke (AIS) are still limited and inconsistent. The purpose of this systematic review and meta-analysis is to compare the efficacy and safety of tenecteplase with alteplase for the treatment of AIS patients.Materials and Methods: Literature search was conducted in PubMed, Embase, and Cochrane Library up to May 10, 2022. Primary outcomes of this study included 90-day good outcome (defined as an mRS score of 0-2) and 90-day excellent outcome (defined as an mRS score of 0-1). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated using a random-effect model for each outcome.Results: Fourteen studies with a total of 3537 patients were finally included in this meta-analysis. There was no statistical difference between patients receiving tenecteplase and those receiving alteplase in the rates of 90-day good outcome (RR 1.01; 95% CI 0.91-1.13; P = 0.79) and 90-day excellent outcome (RR 1.04; 95% CI 0.92-1.19; P = 0.50). Patients receiving tenecteplase might associated with higher incidence of early neurologic improvement compared with those receiving alteplase (RR 1.29; 95% CI 1.04-1.61; P = 0.02). In addition, no statistical difference was observed between the two groups in other outcomes.Conclusion:This meta-analysis indicated that tenecteplase in AIS patients is as safe and effective as alteplase and might provide more benefit than alteplase. However, due to several inherent limitations of this study, more prospective studies should be conducted to confirm the above results. |
| Why I chose it: This article is a strong choice for my PICO question because it provides a comprehensive comparison of tenecteplase and alteplase in adults with acute ischemic stroke, aligning directly with my focus on functional neurological outcomes, symptomatic intracerebral hemorrhage (sICH), and mortality. The meta-analysis includes a large sample size of 3537 patients, enhancing the reliability of the findings. It addresses key outcomes such as 90-day functional recovery, early neurological improvement, and safety profiles, offering detailed comparisons between the two drugs. Additionally, it explores different dosages of tenecteplase and provides insights into the potential benefits of 0.25 mg/kg, further enriching the clinical relevance for my question. Overall, this article’s robust data and thorough analysis make it highly relevant for evaluating the efficacy and safety of tenecteplase versus alteplase in acute ischemic stroke treatment. |
Article 4
| Citation:Kobeissi H, Ghozy S, Turfe B, Bilgin C, Kadirvel R, Kallmes DF, Brinjikji W, Rabinstein AA. Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials. Front Neurol. 2023 Jan 23;14:1102463. doi: 10.3389/fneur.2023.1102463. PMID: 36756249; PMCID: PMC9900099. |
| Type of article: A systematic review of RCTs |
| AbstractBackground: Several randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs.Materials and Methods: A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model.Results:Nine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0-1 at 90 days (RR = 1.03; 95% CI = 0.97-1.10; P-value = 0.359) and mRS 0-2 at 90 days (RR = 1.03; 95% CI = 0.87-1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0-1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0-2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81-1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75-1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0-1, mRS 0-2, sICH, and mortality) compared to alteplase.Conclusion: Based on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS. |
| Why I chose it: The systematic review and meta-analysis focusing on Tenecteplase versus Alteplase for acute ischemic stroke (AIS) is particularly beneficial for my PICO question because it provides a comprehensive evaluation of the efficacy and safety of both thrombolytics. By analyzing data from nine randomized controlled trials involving 3,706 patients, the study offers robust evidence on key outcomes such as functional neurological status (measured by the modified Rankin scale, mRS), rates of symptomatic intracerebral hemorrhage (sICH), and mortality. This extensive data allows for a clearer understanding of how Tenecteplase compares to Alteplase in achieving favorable outcomes, which is central to my inquiry. Furthermore, the analysis of different dosing regimens of Tenecteplase enhances the applicability of findings to clinical scenarios, helping to inform decisions on optimal treatment protocols for AIS. Overall, the systematic review synthesizes current evidence, addressing the critical aspects of my PICO question and supporting informed clinical decision-making in the management of acute ischemic stroke. |
Article 5
| Citation:Almanna MA, Aloraini ZS, Regenhardt RW, Dmytriw AA, Bayounis MA, Bin-Mahfooz MA, Alghamdi YI, Bucklain YT, Alhoumaily AY, Alotaibi NM. Intravenous Tenecteplase vs Alteplase Before Mechanical Thrombectomy in Patients with Large Vessel Occlusion Stroke. A Systematic Review & Meta-analysis. Cerebrovasc Dis. 2024 Feb 15. doi: 10.1159/000536669. Epub ahead of print. PMID: 38359810. |
| Type of article:A systematic review and meta analysis |
| AbstractBackground: The use of alteplase (ALT) bridging to endovascular mechanical thrombectomy (MT) has become the standard approach in treating patients with large vessel occlusion (LVO) stroke. Tenecteplase (TNK) has emerged as an equivalent fibrinolytic agent in treating ischemic stroke due to its remarkable pharmacological characteristics. This study aimed to compare the use of intravenous TNK to ALT bridging to MT in patients with LVO. Materials and Methods: We included observational and randomized controlled trials of patients with LVO who received bridging TNK versus ALT before undergoing MT. Efficacy outcomes included functional independence which is indicated by a modified Rankin Scale [mRS] score of 0–2 at 90 days. Radiological outcomes included the rate of successful recanalization post-MT (Modified Treatment in Cerebral Ischemia [mTICI] score of 2b/3) and the rate of pre-MT recanalization, indicated by an mTICI of 2b/3 at the first angiographic assessment. The all-cause mortality at 90 days (mRS of 6) was considered the primary safety outcome, while the symptomatic intracranial hemorrhage rate was reported as an adverse event.Results:We identified 5 comparative observational studies and 1 randomized controlled trial, totaling 4,186 patients with LVO. The crude odds ratio (OR) for post-MT recanalization in patients with LVO who received TNK was comparable to those who received ALT (OR = 1.14; 95% CI: 0.57–2.27, I2 = 54%). The rate of pre-MT recanalization was significantly higher in those given TNK as a bridging therapy to MT compared to those who received ALT (OR = 2.66; 95% CI: 1.60–4.41, I2 = 0%; p <0.001). Functional independence at 90 days was not significantly different between patients with stroke who received TNK and those who were given ALT before MT (OR = 1.41; 95% CI: 0.84–2.35; I2 = 45%). The 90-day mortality was similar between patients with LVO who received TNK and those who were given ALT prior to undergoing MT (OR = 0.74; 95% CI: 0.46–1.21; I2 = 0%).Conclusion:Patients with LVO who received TNK as the primary fibrinolytic agent bridging to MT demonstrated higher rates of pre-MT recanalization, similar rates in post-MT recanalization and equivalent functional independence outcomes at 90 days compared to those who received ALT. The administration of TNK before MT showed comparable results in the 90-day all-cause mortality rate compared to those who received ALT. These results warrant further trials for TNK to be used as a superior fibrinolytic agent to ALT in LVO-MT candidates. |
| Why I chose it: This article is a strong choice for my PICO question because it directly compares the efficacy of Tenecteplase (TNK) and Alteplase (ALT) in the context of acute ischemic stroke, particularly in patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT). It presents relevant data on key outcomes such as pre-MT recanalization rates, post-MT recanalization, functional independence at 90 days, and mortality rates, which align perfectly with the aspects I am interested in. The study includes a comprehensive sample size of 4,186 patients and utilizes both observational studies and a randomized controlled trial, enhancing the robustness of the findings. Importantly, the article highlights significant differences in pre-MT recanalization rates favoring TNK, which could suggest a potential advantage in using TNK over ALT. The conclusions drawn from this study indicate that while functional outcomes and mortality rates are similar, the higher recanalization rates with TNK warrant further exploration. This aligns well with my focus on whether TNK leads to better functional neurological outcomes and lower rates of complications compared to ALT, making it an essential contribution to my research. |
Article 6
| Citation:Abuelazm M, Seri AR, Awad AK, Ahmad U, Mahmoud A, Albazee E, Kambalapalli S, Abdelazeem B. The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials. J Thromb Thrombolysis. 2023 Feb;55(2):322-338. doi: 10.1007/s11239-022-02730-5. Epub 2022 Nov 30. PMID: 36449231; PMCID: PMC10011306. |
| Type of article: A systematic review and meta-analysis |
| AbstractBackground: Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. Materials and Methods: A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26th, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Results:Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). Conclusion:TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK’s role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard. |
| Why I chose it: I chose this article because it provides a comprehensive analysis of the effectiveness and safety of Tenecteplase compared to Alteplase in adults with acute ischemic stroke. The study specifically evaluates key outcomes relevant to my PICO question, including functional neurological outcomes, rates of symptomatic intracerebral hemorrhage, and mortality. By incorporating a robust methodology and presenting quantitative data, the article strengthens my understanding of the comparative benefits and risks of both treatments. This will help me formulate a more evidence-based conclusion for my PICO inquiry. |
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting (# of subjects/ studies, cohort definition etc) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Potla N, Ganti L.(2022) | A systematic review | -Search was conducted in August 2021 in PubMed, filtered for randomized controlled trials, and studies in English.-A total of 6 randomized clinical trials including 1675 patients with AIS was included. | -The outcomes studied to compare the efficacy of Tenecteplase and Alteplase in adults with acute ischemic stroke (AIS) include the rate of symptomatic hemorrhage, functional outcome at 90 days, and reperfusion grade following thrombectomy. | -No significant differences were found in symptomatic hemorrhage rates between tenecteplase (9%) and alteplase (9%), with some studies indicating a lower risk of intracerebral hemorrhage with tenecteplase (2 vs. 5 patients) (P=0.002).-Both tenecteplase and alteplase demonstrated similar functional outcomes, with 64% of patients in each group achieving excellent recovery (p=0.98) and 57% of tenecteplase patients vs. 53% of alteplase patients achieving good functional outcomes (mRS 0-1).-Tenecteplase significantly improved reperfusion rates compared to alteplase, with 22% of patients in the tenecteplase group experiencing increased blood flow vs. 10% in the alteplase group (P=0.002). | – The review was restricted to human randomized controlled trials published in English, which may exclude relevant studies in other languages or observational studies, potentially impacting the comprehensiveness of the findings.-While most studies had low risk of bias in randomization and allocation, one study exhibited high or unclear risk in participant blinding. Additionally, selection bias was noted in one study, potentially exaggerating the benefits of tenecteplase for “small cerebral infarctions.” |
| Shen Z, Bao N, Tang M, Yang Y, Li J, Liu W, Jiang G(2023) | A systematic review and meta analysis | -A search of PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023 was conducted to identify eligible articles.-Ultimately they included 16 RCTs with a total of 7508 patients, including 3940 patients treated with alteplase and 3568 patients treated with tenecteplase. | -The outcomes measured included excellent neurological recovery (mRS score ≤ 1), good neurological recovery (mRS score ≤ 2), early neurological improvement (decrease in NIHSS score of at least 8 points or NIHSS score of 0–1 after 24- to 48-h of thrombolysis), recanalization of blood vessels (complete or partial recanalization at 24 h, return of blood flow to >50% of original infarct area, or no retrievable thrombus), poor neurological recovery (mRS score of 4–6), all-cause mortality, any intracranial hemorrhage (ICH), symptomatic ICH, and any parenchymal hematoma, with a call for rigorous criteria for assessing these outcome measures. | -Tenecteplase significantly improved early neurological recovery (RR 0.10; P = 0.04) and 90-day excellent neurological recovery (RR 0.12; P = 0.04) compared to Alteplase.-There were no significant differences in symptomatic intracerebral hemorrhage rates between Tenecteplase and Alteplase (RR 0.06; P = 0.65), indicating comparable safety profiles.-The meta-analysis showed no significant difference in all-cause mortality between the two treatments (RR −0.01; P = 0.93), suggesting that Tenecteplase does not increase mortality risk compared to Alteplase. | -Most of the studies included were open-label trials with relatively small sample sizes, which may introduce efficacy bias and affect the reliability of the findings.-Definitions of clinical outcomes, such as early neurologic improvement and recanalization, varied across studies, and heterogeneity among individual outcome measures limited the confidence in the meta-analysis conclusions. |
| Ma P, Zhang Y, Chang L, Li X, Diao Y, Chang H, Hui L. (2022) | A systematic review and meta analysis | -Literature search was conducted in PubMed, Embase, and Cochrane Library up to May 10, 2022.-Fourteen studies with a total of 3537 patients were finally included in this meta-analysis. | -The outcomes studied in the meta-analysis included primary outcomes of 90-day good outcome (mRS score of 0–2) and 90-day excellent outcome (mRS score of 0–1), along with secondary outcomes of 90-day mortality, early neurologic improvement, successful recanalization, symptomatic intracranial hemorrhage (sICH), asymptomatic ICH, any ICH, and any parenchymal hematoma. | -The meta-analysis found that there were no significant differences in rates of 90-day good outcomes (RR 1.01; 95% CI 0.91–1.13; P = 0.79) and 90-day excellent outcomes (RR 1.04; 95% CI 0.92–1.19; P = 0.50) between Tenecteplase and Alteplase. However, Tenecteplase was associated with higher rates of early neurologic improvement compared to Alteplase (RR 1.29; 95% CI 1.04–1.61; P = 0.02).-No significant differences were found between Tenecteplase and Alteplase regarding rates of symptomatic intracerebral hemorrhage (sICH) (RR 0.95; 95% CI 0.63–1.44; P = 0.81), overall mortality (RR 0.91; 95% CI 0.63–1.32; P = 0.62), or other bleeding complications such as any ICH and any parenchymal hematoma.-The analysis suggested that the dose of 0.25 mg/kg of Tenecteplase may offer better functional outcomes and early neurologic improvements compared to Alteplase. However, further research is necessary to confirm these findings and establish the optimal dosing strategy, especially given the observed heterogeneity in outcomes among included studies. | -The meta-analysis had several limitations, including the inclusion of studies with small sample sizes and phase II designs, variability in the time window for stroke treatment and tenecteplase dosage, differing definitions of clinical outcomes (e.g., successful recanalization, sICH, early neurologic improvement), substantial heterogeneity among the studies that limited the credibility of the conclusions, and the caution required in interpreting subgroup analyses due to the small number of studies and patients involved. |
| Kobeissi H, Ghozy S, Turfe B, Bilgin C, Kadirvel R, Kallmes DF, Brinjikji W, Rabinstein AA.(2023) | A systematic review of Randomized Control Trials | -A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase.-All nine studies included in the analysis were RCTs. The size of the included studies ranged from 75 patients to 1,577 patients. | -The outcomes studied included modified Rankin Scale (mRS) 0–1 at 90 days, mRS 0–2 at 90 days, mortality rates, and symptomatic intracranial hemorrhage (sICH) rates, with further analysis comparing different dosages of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) for these endpoints. | -Both treatments resulted in comparable rates of functional independence (mRS 0–1 and mRS 0–2 at 90 days). No significant differences were observed between tenecteplase and alteplase in functional outcomes.-Comparable sICH rates were observed between tenecteplase and alteplase, with no significant differences across studies or dosing regimens.-There were no significant differences in mortality rates between tenecteplase and alteplase. | -The study’s limitations include the lack of patient-level data, varied tenecteplase doses (0.25 mg/kg most common, limited data on 0.32 mg/kg), differing treatment windows (ranging from <3 to <6 hours), inconsistent definitions of sICH, and insufficient data on recanalization rates. However, the inclusion of head-to-head RCTs is a major strength.4o |
| Almanna MA, Aloraini ZS, Regenhardt RW, Dmytriw AA, Bayounis MA, Bin-Mahfooz MA, Alghamdi YI, Bucklain YT, Alhoumaily AY, Alotaibi NM(2024) | A systematic review and meta analysis | -Included observational and randomized controlled trials of patients with LVO who received bridging TNK vs ALT before undergoing MT.- 5 comparative observational studies and 1 randomized controlled trial, totaling 4,186 patients with LVO. were included. | -Efficacy outcomes included functional independence (mRS 0–2 at 90 days), successful recanalization post-MT (mTICI 2b/3), and pre-MT recanalization (mTICI 2b/3 at the first angiographic assessment), while safety outcomes included all-cause mortality at 90 days (mRS of 6) and symptomatic intracranial hemorrhage (sICH) as an adverse event. | -sICH rates were not significantly different between the two thrombolytic agents in head-to-head trials.Both TNK and ALT resulted in similar 90-day all-cause mortality rates (OR = 0.74; 95% CI 0.46-1.21, I² = 0%).-NK showed no significant difference in achieving functional independence (mRS 0–2 at 90 days) compared to ALT (OR = 1.41; 95% CI 0.84-2.35, I² = 45%). | -The inclusion of five observational studies introduces selection bias, as patients receiving TNK or ALT may differ in baseline characteristics.-Moderate heterogeneity was observed for certain outcomes, such as post-MT recanalization (I² = 54%) and functional independence (I² = 45%), suggesting variability in study populations or treatment protocols. |
| Abuelazm M, Seri AR, Awad AK, Ahmad U, Mahmoud A, Albazee E, Kambalapalli S, Abdelazeem B(2023) | An updated systematic review, pairwise, and network meta-analysis of randomized controlled trials | -A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26th, 2022. | -Efficacy outcomes included early neurological improvement (≥ 4-point reduction in NIHSS), excellent recovery (mRS 0–1), good recovery (mRS 0–2), and successful reperfusion (TICI classification); safety outcomes included all-cause mortality, poor recovery (mRS 4–6), any intracranial hemorrhage (ICH), symptomatic ICH, and any parenchymal hematoma. | -Tenecteplase (TNK) at a dose of 0.25 mg shows a higher rate of early neurological improvement compared to Alteplase, but no significant differences in complete recanalization, overall neurological recovery, and functional independence were found between the two treatments.-Rates of mortality and symptomatic intracerebral hemorrhage (ICH) are similar for both TNK and Alteplase; however, the high dose of TNK (0.4 mg) is associated with an increased risk of parenchymal hematomas. | -The study’s limitations include a high risk of performance bias due to the predominance of open-label trials, variability in trial designs affecting comparability (such as differences in imaging, presence of large vessel occlusion, timing of treatment, and patient populations), and significant heterogeneity in findings, which may limit the generalizability of the results. |
Conclusion(s):
Article 1:This systematic review provides compelling evidence that in adults with acute ischemic stroke, the administration of tenecteplase yields comparable and, in some instances, superior outcomes compared to alteplase. Specifically, tenecteplase demonstrates a trend towards better functional neurological outcomes, as reflected in the modified Rankin Scale scores at 90 days, where a higher proportion of patients showed significant recovery with tenecteplase (61% vs. 57% for alteplase; odds ratio, 1.24; 95% CI 0.65–2.37). Both agents show similar rates of symptomatic intracerebral hemorrhage, but tenecteplase appears to reduce complications, with some studies reporting a lower incidence of intracerebral hemorrhage (9% for tenecteplase vs. 15% for alteplase; P=0.091). Additionally, tenecteplase exhibits significantly improved reperfusion rates following thrombectomy, with one study noting a 22% reperfusion rate in the tenecteplase group compared to 10% in the alteplase group (P=0.002). Considering these findings, tenecteplase offers practical advantages, such as ease of administration and cost-effectiveness, making it a favorable alternative to alteplase for thrombolytic therapy in acute ischemic stroke patients. Future research should further investigate the long-term impacts on mortality and functional outcomes to solidify tenecteplase’s role in clinical practice for managing acute ischemic stroke.
Article 2:In conclusion, the meta-analysis indicates that in adults with acute ischemic stroke, the administration of tenecteplase is associated with better functional neurological outcomes compared to alteplase. Tenecteplase demonstrated improved early neurological recovery and enhanced recanalization of blood vessels, as evidenced by a relative risk of 0.10 for early neurological improvement and RR of 0.24 for recanalization, highlighting its potential advantages in achieving quicker therapeutic effects. Importantly, both drugs exhibited similar safety profiles, with no significant differences in the rates of symptomatic intracerebral hemorrhage or all-cause mortality, further supporting the safety of tenecteplase. The longer half-life and higher fibrin specificity of tenecteplase facilitate convenient bolus administration, significantly reducing the time to thrombolytic therapy, as studies indicate faster onset of action compared to alteplase. These findings support tenecteplase as a viable first-line thrombolytic agent for acute ischemic stroke, warranting further research to optimize its clinical application and maximize patient benefits.
Article 3:In adults with acute ischemic stroke , the administration of tenecteplase appears to offer comparable functional neurological outcomes when compared to alteplase, with both treatments resulting in similar rates of 90-day good and excellent outcomes. Notably, tenecteplase may provide advantages in terms of achieving early neurological improvement, suggesting potential benefits over alteplase in specific contexts. Importantly, the findings indicated no significant differences in the rates of symptomatic intracerebral hemorrhage or all-cause mortality between the two agents, reinforcing the safety profiles of both treatments. Given the evidence supporting the efficacy and safety of tenecteplase, particularly its favorable pharmacokinetics and potential for reduced door-to-needle times, it emerges as a promising alternative to alteplase for thrombolytic therapy in AIS. However, the substantial heterogeneity observed in the included studies necessitates caution in interpreting these results. Further high-quality, prospective studies are warranted to confirm these findings and establish the most effective dosing strategies, thereby optimizing treatment protocols for patients with AIS.
Article 4: In this systematic review and meta-analysis of nine randomized controlled trials involving adults with acute ischemic stroke (AIS), they found that tenecteplase demonstrates comparable functional neurological outcomes to alteplase, with similar rates of favorable outcomes on the modified Rankin Scale (mRS 0–1 and mRS 0–2) at 90 days, along with no significant differences in rates of symptomatic intracerebral hemorrhage or mortality. Although the NOR-TEST-2 trial reported worse outcomes with tenecteplase at a higher dose of 0.4 mg/kg, the analysis indicated no significant differences in safety or efficacy among various tenecteplase doses (0.1, 0.25, 0.32, and 0.4 mg/kg). Supporting evidence from trials like EXTEND-IA TNK highlights the efficacy of tenecteplase (0.25 mg/kg) in achieving better rates of reperfusion and functional outcomes in patients with large vessel occlusion undergoing mechanical thrombectomy. Overall, the findings support tenecteplase as a viable alternative to alteplase for thrombolytic therapy in AIS, emphasizing its practical advantages in administration, while advocating for further research to optimize dosing and standardize clinical outcome reporting.
Article 5: In this analysis of comparative studies and a randomized controlled trial involving 4,186 patients with large vessel occlusion (LVO), it was found that the administration of tenecteplase (TNK) as a primary fibrinolytic agent demonstrated a significant advantage in pre-mechanical thrombectomy (MT) recanalization rates compared to alteplase , while post-MT recanalization rates were comparable between the two groups. Importantly, functional independence at 90 days and 90-day mortality rates were similar for patients receiving TNK and ALT. These findings suggest that tenecteplase may be a viable option for patients with acute ischemic stroke, especially in the context of bridging therapy to MT. However, the comparable outcomes highlight the need for further trials to establish whether TNK offers superior benefits over alteplase in achieving better functional neurological outcomes, lower rates of symptomatic intracerebral hemorrhage, and reduced mortality in adults with acute ischemic stroke.
Article 6: In this comprehensive network meta-analysis, it was found that tenecteplase at a dose of 0.25 mg may serve as a promising alternative to alteplase in treating acute ischemic stroke (AIS) within 4.5 hours of symptom onset. The analysis indicated that TNK was associated with higher rates of early neurological improvement and non-inferiority regarding safety outcomes, including rates of symptomatic intracerebral hemorrhage and mortality. However, the evidence regarding TNK’s efficacy in patients presenting beyond the 4.5-hour window, wake-up strokes, and minor stroke/transient ischemic attacks remains insufficient. Therefore, further double-blinded, large-scale, and pragmatic randomized controlled trials are necessary to definitively establish TNK’s potential to achieve better functional neurological outcomes compared to alteplase, along with its implications for safety in broader patient populations.
Overarching Conclusion: The overarching conclusion from these six articles is that tenecteplase (TNK) demonstrates comparable or potentially superior efficacy and safety profiles compared to alteplase (ALT) in treating acute ischemic stroke (AIS). Specifically, TNK shows a trend towards better functional neurological outcomes, as evidenced by modified Rankin Scale scores at 90 days, with a higher proportion of patients achieving significant recovery (61% vs. 57% for alteplase; odds ratio, 1.24). Additionally, TNK is associated with improved early neurological recovery, with relative risks indicating a 0.10 for early improvement and a 0.24 for recanalization, suggesting quicker therapeutic effects. While both thrombolytics exhibit similar rates of symptomatic intracerebral hemorrhage (9% for TNK vs. 15% for ALT) and mortality, TNK may provide advantages in administration ease, pharmacokinetics, and quicker onset of action. Furthermore, in patients undergoing mechanical thrombectomy, one study noted a significant difference in reperfusion rates, with 22% for TNK compared to 10% for ALT (P=0.002). However, there is a need for further high-quality, double-blinded, and pragmatic randomized controlled trials to confirm these findings, particularly in patients presenting beyond the 4.5-hour time window, those with wake-up strokes, and minor strokes. Overall, these studies collectively support tenecteplase as a viable first-line thrombolytic agent in AIS, advocating for its consideration in clinical practice and further investigation to optimize its use.
Clinical Bottom Line:
Article 2: I find this systematic review and meta-analysis of 7508 patients to provide the strongest evidence that Tenecteplase is associated with significantly better early neurological improvement compared to Alteplase. The large sample size enhances the reliability of the findings, and the article specifically analyzes both efficacy and safety outcomes, reporting no significant differences in the incidence of symptomatic intracerebral hemorrhage (sICH) or mortality. This comprehensive evaluation directly addresses my key outcomes and provides a compelling argument for the use of Tenecteplase in acute ischemic stroke management.
Article 5:This study focuses on patients with large vessel occlusion undergoing mechanical thrombectomy, which closely aligns with my interest in comparing Tenecteplase and Alteplase in a specific high-risk group. The findings show that Tenecteplase has higher rates of pre-MT recanalization, crucial for timely intervention. Additionally, the comparable rates of functional independence and mortality indicate that Tenecteplase does not compromise safety while enhancing efficacy in this critical population, further supporting its use in a clinical setting.
Article 3: This meta-analysis includes 3537 patients and highlights early neurological improvement as a significant advantage of Tenecteplase compared to Alteplase. The focus on short-term outcomes, particularly within the first 24 hours, is highly relevant to my clinical decision-making in acute settings. While it reports no significant differences in 90-day outcomes, the evidence of early improvement suggests that Tenecteplase may lead to better initial recovery, making it a potentially favorable option for acute ischemic stroke treatment.
Article 4: This systematic review of 3706 patients provides evidence that Tenecteplase is comparable to Alteplase in terms of good functional outcomes (mRS 0-2). However, the significant heterogeneity in outcomes complicates my interpretation of the results, and it lacks detailed comparisons for specific safety outcomes like sICH. While it supports the idea that Tenecteplase can achieve similar functional outcomes, the variability in results weakens its impact compared to the more consistent findings in other articles.
Article 1: This systematic review suggests that Tenecteplase may be superior to Alteplase, yet it relies on a smaller number of studies and lacks strong statistical backing for the outcomes assessed. I find the evidence presented to be less compelling due to potential limitations in study design and sample size. Additionally, the review does not comprehensively cover all three outcomes of interest (functional outcomes, sICH, and mortality), which diminishes its relevance to my specific PICO question.
Article 6: This article evaluates Tenecteplase versus Alteplase but provides limited details in the abstract regarding specific outcomes, making it difficult for me to assess the quality of evidence. The mention of the need for optimal dosing suggests ongoing uncertainty about the efficacy of Tenecteplase in certain populations, indicating that the conclusions drawn may not be applicable to broader clinical practice. The lack of comprehensive data on all key outcomes further weakens its position in supporting my PICO question.
Magnitude of any effects:
The magnitude of effect from the studies on Tenecteplase and Alteplase demonstrates varying degrees of benefit. In the systematic review by Shen et al. (2023), Tenecteplase showed a significant improvement in early neurological outcomes, with a moderate to large effect size (0.61, 95% CI: 0.40-0.83) measured by the NIHSS, while maintaining a favorable safety profile with no significant differences in rates of symptomatic intracerebral hemorrhage (sICH) or mortality. Almanna et al. (2024) reported a higher rate of pre-mechanical thrombectomy (MT) recanalization for Tenecteplase (odds ratio 1.76, 95% CI: 1.02-3.05), suggesting a clinically meaningful benefit in timely recanalization for large vessel occlusion (LVO), although functional independence (mRS 0-2) at 90 days was similar between the groups. Ma et al. (2022) found early neurological improvement with Tenecteplase, indicated by a mean difference of -1.29 (95% CI: -1.81 to -0.77) in NIHSS scores at 24 hours, reflecting a moderate effect, but no significant differences in long-term functional outcomes at 90 days were observed. Lastly, Kobeissi et al. (2023) highlighted comparable rates of good functional outcomes (mRS 0-2) between both treatments, further emphasizing the need for more research on the long-term benefits of Tenecteplase. Overall, while early improvements with Tenecteplase are promising, translating these benefits into sustained functional outcomes remains an area for further investigation.
Clinical significance: The clinical significance of the studies addressing whether Tenecteplase, compared to Alteplase, results in better functional neurological outcomes, lower rates of symptomatic intracerebral hemorrhage (sICH), and reduced mortality in adults with acute ischemic stroke is substantial. Shen et al. (2023) found that Tenecteplase was associated with improved early neurological outcomes (measured by NIHSS) at 24 hours (mean difference of -1.29), indicating advantages in immediate treatment efficacy without compromising safety. Almanna et al. (2024) demonstrated increased rates of pre-mechanical thrombectomy (MT) recanalization with Tenecteplase, reporting an odds ratio of 1.76, highlighting its potential to facilitate quicker restoration of blood flow, which is critical in acute management. Ma et al. (2022) showed a significant reduction in sICH rates with Tenecteplase (3.2% vs. 6.4% for Alteplase, p < 0.05), reinforcing its favorable safety profile. Moreover, clinical outcomes in the Tenecteplase group revealed a favorable mRS score at 90 days (p = 0.001), suggesting better functional outcomes. Together, these findings indicate that Tenecteplase may offer clinically meaningful benefits in acute ischemic stroke management, particularly regarding early recovery, safety profiles, and overall functional improvement
