Abstract
Background:
Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15–20% of acute stroke with large vessel occlusion.
Aims:
We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL.
Methods:
This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0–1. Secondary outcomes were mRS 0–2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b–3) on first and successful reperfusion (eTICI 2b–3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed.
Results:
Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0–1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06–9.71) compared with alteplase. No statistically significant differences in rates of mRS 0–2 (aOR 1.53; 95% CI = 0.51–4.55), initial rAOL 2b–3 (16.3% vs. 28.6%), final eTICI 2b–3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group.
Conclusion:
In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.
Keywords: Stroke, endovascular, tandem, tenecteplase
Introduction
Tandem cervical carotid lesions (⩾70% carotid stenosis or occlusion with ipsilateral intracranial occlusion) account for about 15–20% of acute ischemic stroke patients with large vessel occlusions (LVO).1–4
The optimal management of the tandem lesion, and the outcome of these patients have been investigated in several observational studies, with at least three ongoing randomized clinical trials (TITAN NCT03978988, EASI-TOC NCT04261478, and PICASSO NCT05611242) to address the uncertainty of how to acutely treat these patients before and during endovascular thrombectomy (EVT).5–9 Prior studies comparing EVT alone with combined EVT and intravenous alteplase in tandem lesion patients, have reported better functional outcomes and reperfusion grades with combined therapy without an increased risk of intracranial bleeding, including when acute carotid stenting was performed.10–12 This suggests that pre-EVT intravenous thrombolysis (IVT) with alteplase is beneficial and safe in patients with tandem carotid lesion. However, the impact of using intravenous tenecteplase versus alteplase prior to EVT in this subgroup of patients has not been extensively studied. 13
We therefore chose to compare the safety and efficacy of intravenous tenecteplase versus alteplase in acute stroke patients with tandem carotid lesions in both the EVT + IVT and IVT-only groups, from the Alteplase versus Tenecteplase randomized controlled trial (AcT). This was the first Phase 3 randomized controlled trial comparing tenecteplase (0.25 mg/kg) with alteplase in patients with acute ischemic stroke eligible for thrombolysis. 14 In addition, we compared the effect of tenecteplase versus alteplase in patients with tandem lesions undergoing acute cervical internal carotid artery (ICA) stenting.
Our hypothesis is that in patients with symptomatic high-grade (⩾70%) stenosis or occlusion of the cervical ICA ipsilateral to their stroke, the use of intravenous tenecteplase will result in comparable safety and efficacy compared with intravenous alteplase.
Method
Patient population
This is a post hoc analysis of the AcT trial, which was a pragmatic, randomized, controlled, open-label registry-linked trial with blinded outcome assessment, assessing the noninferiority of intravenous tenecteplase compared with alteplase in patients with acute ischemic stroke eligible for thrombolysis.14,15
Inclusion and exclusion criteria of the AcT trial have been reported previously.14,16 Broadly, patients ⩾18 years old with suspected diagnosis of acute ischemic stroke and presenting within 4.5 h of symptom onset were included. Patients eligible for EVT were also included. Included patients were randomly assigned (1:1) to either intravenous tenecteplase (0.25 mg/kg of body weight) or intravenous alteplase (0.9 mg/kg of body weight).
The current analysis included the subgroup of patients with tandem carotid lesions, which were defined as ⩾70% stenosis or occlusion of the extracranial ICA and concomitant occlusion of the intracranial ICA, M1 or M2 segments of middle cerebral artery (MCA) assessed on baseline computed tomography angiography (CTA). We used this definition as it is the one most commonly used in the literature (French stroke registry (ETIS 10 ), German stroke registry (GSR 17 ), the EXTEND-IA TNK trials, 13 a meta-analysis of 33 studies, 18 and the ongoing trials EASI-TOC NCT04261478 and PICASSO NCT05611242).
The M2 segment was defined as the segment extending from the first bifurcation of the proximal MCA excluding the temporopolar branch to the circular sulcus of the insula. 19 Patients without intracranial occlusion or baseline CTA, with vertebrobasilar, isolated cervical ICA, or distal occlusion (M3/M4 segment of the MCA were excluded (Figure 1).
Figure 1.
Study flow chart.
Indications for EVT followed institutional and Canadian Best Practices guidelines. 20 The trial was regulated by Health Canada, approved by research ethics boards at each participating center and used deferred consent procedures at sites where this was allowed. This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines (see STROBE in the Supplemental material).
Imaging assessment
All imaging data (baseline noncontrast computed tomography (CT), CT angiography of head and neck, digital subtraction angiography, follow-up imaging) were reviewed by the trial imaging core laboratory. The readers were blinded to treatment allocation and clinical outcomes.
The degree of stenosis of the cervical ICA was assessed on baseline CTA according to NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteria and graded as 0–29% stenosis, 30–49% stenosis, 50–69% stenosis, 70–89% stenosis, or ⩾90% stenosis and complete occlusion. 21 In addition, extracranial ICA was reviewed for degree of stenosis on the first neck angiographic acquisition of the carotid artery in patients who underwent EVT. Of note, pseudo-occlusions due to terminal ICA occlusion were seen in 15 cases on CTA and the diagnosis was adjusted after reading the digital subtraction angiography (DSA) images.
Treatment of the extracranial ICA lesion (i.e. acute stenting or not) and sequence of treatment (intracranial-first vs. extracranial-first approach) were left to the discretion of the treating team. Reperfusion grade was assessed on the first and final angiographic run of the thrombectomy procedure using the expanded Thrombolysis in Cerebral Infarction Score (eTICI). Recanalization of intracranial thrombus was assessed using the revised arterial occlusion scale (rAOL) scale on the initial angiographic run of EVT.22,23 Standard of care imaging at 24 h after thrombolysis administration was assessed for any intracranial hemorrhage (ICH) and classified using the Heidelberg classification. 24
Outcomes measures
The primary outcome was assessed at 90 days, and up to 120 days after randomization (modified Rankin Scale (mRS) score of 0–1) through standardized telephone interviews conducted centrally by blinded trained research coordinators using the Rankin Focused Assessment. 25 Secondary outcomes were 90–120-day mRS score of 0–2, shift along the full mRS scale at 90–120 days, return to baseline function at 90 days, successful recanalization (rAOL score of 2b–3) and successful reperfusion (eTICI score of 2b–3) at first angiographic acquisition in patients taken for EVT, final successful reperfusion at final angiographic acquisition (eTICI score of 2b-3), and length of hospital stay.
Key safety outcomes were 90-day all-cause mortality, procedural complications and symptomatic ICH defined as ICH that was temporally related to and directly responsible for worsening of the patient’s neurological condition and in the investigator’s opinion, was the most important factor for the neurological worsening.
Statistical analyses
Baseline characteristics, imaging variables, and outcomes were compared between intravenous treatment groups (tenecteplase vs. alteplase) in patients with tandem lesion. Analyses were divided into patients treated with combined therapy (EVT + IVT) and patients treated with IVT alone.
Categorical variables were expressed as frequencies and percentages, quantitative variables as mean (standard deviation (SD)) for normal distribution, or median (interquartile range (IQR)) for non-normal distribution. Fisher’s exact test was used for categorical data and Student t-test or Wilcoxon rank sum test for continuous variables.
Adjusted analyses for functional outcomes were conducted using mixed-effects logistic regression. Fixed-effects covariates were age, baseline NIHSS score, stroke onset-to-arterial access time, and occlusion location at baseline (ICA, M1-MCA, and M2-MCA), and participating site was included as a random-effects variable to account for clustering within each site. Thrombolysis treatment by tandem lesion interaction was assessed by using multiplicative interaction terms in the mixed-effects logistic models of mRS 0–1, mRS 0–2, ordinal analysis of mRS, and death at 90 days. Effect size estimates were reported as adjusted odds ratios (aORs) with their 95% confidence intervals (95% CI) or adjusted common OR for a 1-step shift toward better functional outcome. For ordinal regression, mRS 5 and 6 were combined and the Brant test was used to assess the proportional odds assumption.
Furthermore, we reported the outcomes in the tandem EVT group for patients who underwent cervical carotid stenting versus those who did not, using descriptive statistics, and assessed for effect modification of stenting on the relationship between thrombolysis treatment type and functional outcomes using the Mantel Haenszel test.
No imputation was performed as missing data were minimal. No correction for multiple testing was done as all secondary analyses were considered exploratory.
Statistical significance was defined as two-tailed p < 0.05. All analyses were performed using Stata/MP 17.0 (STATA LLC, Corp).
Results
Among 1577 AcT patients, 682 had intracranial ICA, M1-MCA or M2-MCA occlusions. Carotid tandem lesions were seen in 128/682 (18.8%), and 10/128 (7.8%) had occlusions due to cervical carotid dissection (Figure 1).
Among the 128 tandem lesion patients, 93 (72.7%) patients underwent EVT. Compared with patients who underwent EVT, patients who did not undergo EVT were older (median 77 years (IQR 65–87) vs. median 67 years (IQR 58–75), p < 0.01), had lower NIHSS scores (median 10 (IQR 6–18) vs. median 17 (IQR 13–22), p < 0.01), longer delays from stroke symptom onset to thrombolysis initiation (median 142 (111–189) min vs. median 110 (87–149) min, p < 0.01), more often had M2-MCA (18 (51.4%) vs. 18 (19.3%) compared with ICA and M1 occlusions (15 (48.6%) vs. 75 (80.6%) p < 0.01), had a higher prevalence of poor collateral grade at baseline (5 (14.7%) vs. 9 (9.7%) p = 0.52) and higher ASPECTS scores (median 10 (IQR 8–10) vs. median 8 (IQR 7–9), p < 0.01) (Supplemental Table 1). In the EVT subgroup, patients with tandem lesions were younger, more commonly men, and more often had terminal ICA occlusion and lower ASPECTS (Supplemental Table 2).
Tandem patients treated with EVT + IVT (n = 93)
Baseline characteristics were similar between the thrombolysis treatment groups (Table 1).
Table 1.
Baseline characteristics of tandem lesion patients treated with EVT and IVT (n = 93).
| Tenecteplase (n = 50) | Alteplase (n = 43) | p Value | |
|---|---|---|---|
| Baseline characteristics | |||
| Age, median (IQR) | 68 (57–77) | 67 (58–75) | 0.76 |
| Female sex | 19 (38.0) | 11 (25.6) | 0.27 |
| Baseline NIHSS, median (IQR) | 18 (12–23) | 16 (13–21) | 0.50 |
| Workflow times, min | |||
| Time from onset to hospital arrival (n = 92) | 79.5 (64–137) | 76 (53–123) | 0.52 |
| Time from onset to needle (n = 92) | 119 (91–149) | 108 (80–150) | 0.30 |
| Time from onset to arterial access (n = 92) | 167 (147–238) | 155 (121–215) | 0.14 |
| Time from needle to arterial access (n = 92) | 39 (26–62) | 39 (25–69) | 0.86 |
| Time from arterial access to successful reperfusion (n = 84) | 36 (24–51) | 37 (17–54) | 0.70 |
| Type of enrolling center | 0.62 | ||
| Primary stroke center | 3 (6.0) | 1 (2.3) | |
| Comprehensive stroke center | 47 (94.0) | 42 (97.7) | |
| Imaging characteristics | |||
| Occlusion location | 0.77 | ||
| ICA | 18 (36.0) | 18 (41.8) | |
| M1-MCA | 21 (42.0) | 18 (41.9) | |
| M2-MCA | 11 (22.0) | 7 (16.3) | |
| Collateral grade (n = 127) | 0.99 | ||
| Poor | 5 (10.0) | 4 (9.3) | |
| Intermediate | 25 (50.0) | 22 (51.2) | |
| Good | 20 (40.0) | 17 (39.5) | |
| ASPECTS, median (IQR) | 8 (7–9) | 8 (7–9) | 0.55 |
| Tandem lesion type | 0.59 | ||
| 70–89% stenosis | 1 (2.0) | 2 (4.6) | |
| ⩾90% stenosis or occlusion | 49 (98.0) | 41 (95.3) | |
| Dissection | 5 (10.0) | 5 (11.6) | 0.99 |
Data are n (%) or median (IQR).
EVT: endovascular thrombectomy; IVT: intravenous thrombolysis; IQR: interquartile range; NIHSS: National Institutes of Health Stroke Scale; ICA: internal carotid artery; MCA: middle cerebral artery; ASPECTS: Alberta Stroke Program Early CT Score.
Proportions of mRS 0–1 (23 (46.0%) vs. 14 (32.6%), p = 0.21) and mRS 0–2 (27 (54.0%) vs. 25 (58.1%), p = 0.83) at 90–120 days were not significantly different between tenecteplase and alteplase groups, respectively.
In the multivariable analyses adjusted for age, baseline NIHSS score, time from onset to arterial access, and occlusion site, tenecteplase was significantly associated with higher rates of mRS 0–1 (aOR 3.21; 95% CI = 1.06–9.71). However, tenecteplase was not associated with mRS 0–2 (aOR 1.53; 95% CI = 0.51–4.55) or change along the full mRS score (adj. common OR 1.34; 95% CI = 0.61–2.94) (Figure 2).
Figure 2.
Distribution of the modified Rankin Scale scores at 90–120 days in patients with carotid tandem lesion treated with EVT. There was no significant difference between the tenecteplase and alteplase groups in the ordinal analysis of the modified Rankin Scale (mRS) score, adjusted for age, baseline stroke severity, occlusion location at baseline, stroke onset-to-arterial access time as fixed-effects variables, and site as a random-effects variable (adjusted common odds ratio, 1.34 (0.61–2.94)). The modified Rankin Scale score ranges from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability, 3 moderate disability, 4 moderately severe disability, 5 severe disability, and 6 death.
On first intracranial angiographic acquisition, there was no significant difference between the tenecteplase and alteplase groups for successful intracranial recanalization (8 (16.3%) vs. 12 (28.6), p = 0.21) and successful reperfusion (4 (8.2%) vs. 8 (19.0%), p = 0.21). Successful reperfusion on final angiographic run was also similar (41 (83.7%) vs. 36 (85.7%), p = 0.99) (Table 2).
Table 2.
Functional, safety, and angiographic outcomes of tandem lesion patients treated with EVT and IVT (n = 93).
| Tenecteplase (n = 50) | Alteplase (n = 43) | p Value | |
|---|---|---|---|
| Clinical outcomes | |||
| mRS 0–1 at 90–120 days | 23 (46.0) | 14 (32.6) | 0.21 |
| mRS 0–2 at 90–120 days | 27 (54.0) | 25 (58.1) | 0.83 |
| Actual mRS score at 90–120 days | 2 (1–5) | 2 (1–4) | 0.87 |
| Return to baseline function (n = 82) | 10 (22.7) | 12 (31.6) | 0.46 |
| Length of hospital stay, days (n = 87) | 6.5 (3–16) | 9 (4–14) | 0.91 |
| Angiographic outcomes | |||
| Initial run rAOL 2b–3 (n = 91) | 8 (16.3) | 12 (28.6) | 0.21 |
| Initial run eTICI score 2b–3 (n = 91) | 4 (8.2) | 8 (19.0) | 0.21 |
| Final eTICI score 2b–3 (n = 91) | 41 (83.7) | 36 (85.7) | 0.99 |
| Acute cervical ICA treatment | |||
| Stenting with or without balloon angioplasty | 19 (38.0) | 10 (23.3) | 0.18 |
| Balloon angioplasty alone | 26 (52.0) | 20 (46.5) | 0.80 |
| Procedural complications | 3 (6.0) | 0 (0) | 0.25 |
| Vessel perforation | 1 (1.1) | 0 (0) | |
| Intracranial dissection | 0 (0) | 0 (0) | |
| Extracranial dissection | 1 (1.1) | 0 (0) | |
| Emboli to new territory | 0 (0) | 0 (0) | |
| Access site complication | 1 (1.1) | 0 (0) | |
| Safety outcomes | |||
| Death within 90 days of randomization | 9 (18.0) | 7 (16.3) | 0.99 |
| Symptomatic intracerebral hemorrhage | 1 (2.0) | 0 (0) | 0.99 |
| Imaging identified intracranial hemorrhage | 11 (22.0) | 14 (32.6) | 0.35 |
| Subarachnoid hemorrhage | 5 (10.0) | 7 (16.3) | 0.54 |
| Subdural hemorrhage | 0 (0) | 0 (0) | – |
| Intraventricular hemorrhage | 1 (2.0) | 1 (2.3) | 0.99 |
| HI1 (scattered small petechiae) | 3 (6.1) | 1 (2.3) | 0.62 |
| HI2 (confluent petechiae) | 3 (6.1) | 6 (13.9) | 0.30 |
| PH1 (hematoma occupying <30% of infarct with no substantive mass effect) | 1 (2.0) | 3 (7.0) | 0.34 |
| PH2 (hematoma occupying ⩾ 30% of infarct with obvious mass effect) | 1 (2.0) | 1 (2.3) | 0.99 |
| Remote PH | 0 (0) | 0 (0) | – |
| Any PH | 2 (4.0) | 4 (9.3) | 0.41 |
Data are n (%) or median (IQR).
EVT: endovascular thrombectomy; IVT: intravenous thrombolysis; mRS: modified Rankin Scale; rAOL: revised Arterial Occlusive Lesion score; eTICI: extended Thrombolysis in Cerebral Infarction; HI: hemorrhagic infarction; PH: parenchymal hematoma; IQR: interquartile range.
Death at 90–120 days occurred in 9 (18.0%, tenecteplase group) vs. 7 (16.3%, alteplase group), p = 0.99, and aOR was 0.55; 95% CI = 0.13–2.30). There was only one case of symptomatic ICH, which occurred in the tenecteplase group. Rates of intracerebral hemorrhages and procedural complications were comparable between the thrombolysis treatment groups. Parenchymal hemorrhage occurred in two (4.0%) patients in the tenecteplase group versus four (9.3%) in the alteplase group (p = 0.41).
No thrombolysis treatment effect modification by tandem lesion was found for all outcomes (p interaction = 0.09 for mRS 0–1, p = 0.95 for mRS 0–2, p = 0.99 for change along the full mRS, and p = 0.74 for death at 90 days) (Supplemental Table 3).
Acute treatment of the cervical ICA lesion among EVT patients
Stenting of cervical ICA was performed in 29 of the 93 patients who underwent EVT (31.2%); 23/29 (79%) with the intracranial-first approach and 6/29 (21%) with the extracranial-first approach. In stented patients, functional and safety outcomes were similar between the thrombolysis treatment groups except for the rates of subarachnoid hemorrhage and hemorrhagic infarction type 2, which were higher in the alteplase group (Supplemental Table 4).
Among non-stented patients (64/93, 68.8%), 46/64 (72%) underwent balloon angioplasty alone during EVT. Functional and safety outcomes rates were similar between the thrombolysis treatment groups (Supplemental Table 4). The stratified analysis using Mantel Haenszel test did not show evidence of effect modification of stenting on the association of thrombolytic agent used with functional outcomes (p = 0.19 for mRS 0–1 and p = 0.36 for mRS 0–2).
Tandem patients treated with IVT alone (n = 35)
There were 35/128 (27.3%) tandem patients who did not undergo EVT. The rates of functional and safety outcomes were also similar between the thrombolysis treatment groups (Supplemental Table 5).
Discussion
In this post hoc analysis of the AcT trial, we compared the outcomes of patients with carotid tandem lesions treated with intravenous tenecteplase versus alteplase in both the EVT + IVT and IVT-only groups. Tenecteplase was associated with higher rates of mRS 0–1 at 90 days compared with alteplase only in the EVT + IVT group. Safety and angiographic outcomes were not significantly different between the thrombolysis treatment groups.
Tenecteplase is a variant of alteplase, with greater fibrin specificity and prolonged half-life. 26 Its ease of administration as a bolus offers an advantage over alteplase, in particular for patients who need to be transferred to a comprehensive stroke center. Its efficacy and safety were demonstrated in multiple Phase 2 and Phase 3 trials comparing the dose of 0.25 mg/kg with alteplase (0.9 mg/kg).14,27–29 However, data on its efficacy and safety in acute stroke with carotid tandem lesions are limited. In a pooled analysis of the EXTEND-IA TNK trials, 71 patients with carotid tandem lesions treated with EVT were analyzed. Reperfusion on initial angiographic run, 90-day mRS, symptomatic ICH and death rates were similar between the thrombolysis groups. 13
In our study, tenecteplase was associated with increased odds of mRS 0–1 compared with alteplase in the EVT + IVT group, whereas no statistically significant differences were noted for mRS 0–2 and the change along the full range of mRS scores. This may be partly explained by nominally higher rates of early reperfusion in the tenecteplase group. Although not available for this analysis, differences in follow-up infarct volumes may have contributed to the difference in proportions of mRS 0–1. We do not exclude that these results may be subject to type I and II errors because of the small sample size. Larger studies of tenecteplase effect on the incidence of infarcts in new territories and final infarct volumes are warranted.
Rates of symptomatic ICH and parenchymal hemorrhage were not different between the treatment groups in our study, similar to the EXTEND IA-TNK trials, however, the rate of symptomatic ICH was lower in our study (2% (1/50) vs. 7% (4/56)) 13 Among the four patients with symptomatic ICH in the EXTEND IA-TNK pooled analysis, two received tenecteplase 0.40 mg/kg. High dose of tenecteplase (0.40 mg/kg) was associated with poor functional outcomes and an increased risk of bleeding in the NOR-TEST 2 trial. 30 Concomitant stenting of the extracranial carotid artery during EVT was not associated with a higher risk of symptomatic ICH or PH in tenecteplase versus alteplase patients in our study. However, subarachnoid hemorrhage and hemorrhagic infarction type 2 were more common with alteplase.
Optimal management of carotid tandem lesions during EVT is still uncertain. Pre-EVT intravenous alteplase and carotid stenting appear to be safe and associated with better outcomes 10 ; however, the timing of carotid stenting needs to be studied further. The results of ongoing randomized controlled studies will provide us with high-level evidence to improve the outcomes of this patient population.7,8 Our results are in line with the results of the AcT trial, which did not show an increased bleeding risk with tenecteplase. In our study, the rates of ICH and procedural complications were similar between thrombolysis treatment in acutely stented and non-stented patients, which supports the use of tenecteplase as an alternative to alteplase for stroke patients with carotid tandem lesions treated with EVT.
Our study has several limitations. First, this is a post hoc analysis of a randomized trial with a relatively small sample size. However, it is the largest study of carotid tandem lesions patients treated with tenecteplase. Second, only patients treated within 4.5 h from stroke symptom onset were included and therefore our results may not be generalizable to patients treated outside this interval; however, baseline and imaging characteristics of patients included in this study are similar to those included in previous studies beyond the 4.5 h window.4,31 Third, information on use of antiplatelet therapy during or after EVT was not available for this study, and therefore we were not able to assess the effect and safety of tenecteplase according to type, route, and number of administered antiplatelet agents. Fourth, some patients with tandem lesions did not undergo EVT, likely attributable to older age, more distal occlusions, and other pre-existing comorbidities, highlighting the heterogeneity of patient selection for EVT. Although the specific reasons for exclusion from EVT were not collected, the outcomes of this subgroup are of interest to the stroke community as they are rarely reported in the literature. Fifth, the rate of ICA stenting during EVT was low in this study, and therefore no solid conclusions could be drawn from these subgroup results. Sixth, decisions regarding acute cervical ICA treatment and timing of treatment were left to the discretion of treating physician, since there is no consensus on the management of this type of lesion.
Conclusion
In this post hoc subgroup analysis of patients with carotid tandem lesions from the AcT trial treated with EVT comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg), intravenous tenecteplase was associated with higher rates of mRS 0–1. However, rates of mRS 0–2, change along the full mRS scale, angiographic reperfusion rates, and safety outcomes were comparable between alteplase and tenecteplase patients. These results support the use of tenecteplase as an alternative to alteplase in stroke patients with carotid tandem lesions.
Supplemental Material
Supplemental material, sj-pdf-1-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke
Supplemental material, sj-pdf-2-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke
Footnotes
Data availability: Data collected for the study may be made available to others on reasonable request and after signing appropriate data sharing agreements. Such requests must be approved by the respective ethics boards and appropriate data custodians.
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Y.P. is the Principal investigator of the EASI-TOC trial of carotid stenting, partially funded by Stryker, Brain Canada, Heart and Stroke Foundation of Canada, and the Canadian Stroke Consortium and is in the advisory board of and receives speaker honoraria from Roche Canada. Other authors report no conflict of interest.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs: Fouzi Bala 
https://orcid.org/0000-0001-6748-2081
Nishita Singh
https://orcid.org/0000-0003-3647-0904
Ayoola Ademola
https://orcid.org/0000-0002-8412-6246
Shelagh B Coutts
https://orcid.org/0000-0001-5090-5105
Luciana Catanese
https://orcid.org/0000-0002-8696-5211
Dar Dowlatshahi
https://orcid.org/0000-0003-1379-3612
Jay Shankar
https://orcid.org/0000-0002-3707-9723
Thalia S Field
https://orcid.org/0000-0002-1176-0633
Alejandro Manosalva
https://orcid.org/0000-0001-8801-9248
Michael D Hill
https://orcid.org/0000-0002-6269-1543
Michel Shamy
https://orcid.org/0000-0002-0085-6816
Richard H Swartz
https://orcid.org/0000-0001-6571-5531
Alexandre Y Poppe
https://orcid.org/0000-0002-1419-2635
Supplemental material: Supplemental material for this article is available online.
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Supplementary Materials
Supplemental material, sj-pdf-1-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke
Supplemental material, sj-pdf-2-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke