A total of 34 articles were retrieved in this search. Thirty-three articles were considered for this screening, and 28 articles were excluded because the study did not focus on stroke patients (n = 18), the type of study did not meet our inclusion criteria (n = 6), the article came up twice through the search (n = 3), or the study was prematurely terminated (n = 1). Six articles were included in the systematic review. See Fig. 1.
Baselines of patients
In total, the data consisted of 1675 patients treated with intravenous thrombolytics for acute ischemic stroke. A total of 782 patients received tenecteplase while 727 received alteplase (not including 5 because of a lack of specification). Based on the available information, the mean age of the participants across 3 studies was 70.4 years (SD = 14.4) for patients using tenecteplase and 71.3 (SD = 15.9) for patients using alteplase, ranging from 49 to 92 years across all treatments [12,13,14]. All subjects suffered from acute ischemic stroke and were followed up for 90 days. The remaining studies either measured their data using the median or did not provide an age range. One study provided a median age of 71 years between both treatments (IQR = 64–79) . The remaining 1 study did not provide age data .
Risk of bias of included studies
Each of the studies’ randomization, allocation blinding, incomplete outcome data, double-blinding, and other sources of bias were assessed as a low risk of bias in most of the included studies [12, 13, 16]. Blinding of participants scored a high risk or unclear risk in 1 of the studies . A letter to the article describes that the researchers committed selection bias for “small cerebral infarctions” and furthermore exaggerated the benefits of tenecteplase versus alteplase in patients with ischemic stroke . There are some studies where the blinding outcomes were either not described or unclear so they were scored unclear in the detection of bias .
Study objectives did not vary for most of the studies: tenecteplase versus alteplase for acute ischemic stroke [12,13,14,15,16], tenecteplase’s effect on recanalization on patients with ischemic stroke , and most effective time frame to use tenecteplase/alteplase after ischemic stroke . To determine the effectiveness with the current understanding that alteplase can help patients with AIS, tenecteplase was compared with essentially one control group: alteplase [12,13,14,15,16].
All six trials involved a randomized, prospective, open-label, and blinded endpoint trial with prior baseline CT scans to first establish lack of intracerebral hemorrhage [12,13,14,15,16,17]. In five of the trials, thrombolytics were administered within 4.5 h of symptom onset [12,13,14, 16] while in one trial it was within 6 h . Following diagnosis, patients were randomized to the following treatment options: 0.4 mg/kg dose of tenecteplase v. 0.9 mg/kg dose of alteplase [12, 16] or 0.25 mg/kg dose of tenecteplase v. 0.9 mg/kg dose of alteplase [13, 14] or 0.1 mg/kg dose of tenecteplase v. 0.25 mg/kg dose of tenecteplase v. 0.9 mg/kg dose of alteplase . To measure the degree of disability following the stroke treatment, the modified Rankin Score (mRS) was used as the main metric in five studies [12, 13, 15]. The mRSis a 6-point disability scale where 0 means no disability and 6 means dead.
Patients were not informed of treatment allocation. Within 24–48 h of treatment, symptomatic intracranial hemorrhage and intracranial hemorrhage were ascertained [12,13,14,15,16]. Other studies additionally tested for reperfusion rates within 24 to 48 h [13, 15].
Qualitative synthesis: outcome
The included studies (Table 2) show that tenecteplase is either better or has an equivalent effect as alteplase on patients with AIS.
Rate of symptomatic hemorrhage
Four trials showed insignificant differences in the percentage of patients with symptomatic hemorrhage [12,13,14, 16]. All studies noted that there would need for additional tests to conclude that treatment with a certain dose of tenecteplase exposes patients to a higher risk of bleeding complications than alteplase does and vice versa. Logallo et al. note any hemorrhage occurred in 9% of patients taking tenecteplase and also 9% of patients taking alteplase (P=0.82) . Campbell et al. reported intracranial hemorrhage rates were 15% for tenecteplase patients versus 29% for alteplase patients (P=0.091) . It may be important to note that Logallo et al. utilized a 0.4 mg/kg dose of tenecteplase and Campbell et al. utilized a 0.25 mg/kg dose of tenecteplase. Huang et al. do not mention intracranial or symptomatic hemorrhage as one of their outcomes, therefore goes unmentioned during the review. Ronning et al. conclude that tenecteplase in fact had a significant effect in reducing symptomatic hemorrhage in comparison to alteplase. Specifically, intracerebral hemorrhages only impacted 2 of the 75 patients in the tenecteplase pool and 5 of the 71 patients in the alteplase (P=0.002) . It is important to note that alteplase does not exceed the function or utility of tenecteplase; however, tenecteplase is either equivalent or better than the function of alteplase.
Functional outcome at 90 days
Two studies reported on functional outcome, and there was no statistically significant difference between tenecteplase and alteplase. Logallo et al. identified an excellent functional outcome for 64% of the patients in the tenecteplase pool and 64% of the patients in the alteplase pool (p=.98) . Roning et al. show insignificance as well with 57% of patients that received tenecteplase and 53% of patients that received alteplase attained a good functional outcome (mRS 0-1) at 90 days .
Reperfusion rate after thrombectomy
In three trials, the criteria of “reperfusion rates after thrombectomy” was not mentioned, quantified, or the focus of their papers [12, 14, 16]. In the remaining three studies, tenecteplase was superior at increasing the reperfusion rate after thrombectomy. Campbell et al. reported 22% of the patients in the tenecteplase group and 10% of the patients in the alteplase group saw an increase in blood flow in the formerly blocked artery (P=0.002) . Parsons et al. report reperfusion rates were significantly better for patients treated with tenecteplase (P=0.004) . Ronning et al. confirmed these findings by concluding that tenecteplase increased recanalization better than alteplase .