US Pharm. 2022;47(10):HS-10-HS-13.
ABSTRACT: To evaluate the safety, time, and cost savings associated with using tenecteplase versus alteplase for the management of acute ischemic stroke, a single-center, retrospective chart review was conducted in adult patients who received either tenecteplase or alteplase for the treatment of an acute ischemic stroke at CHI Memorial Hospital. Six months of alteplase data were compared with 6 months of tenecteplase data, and the primary endpoints were median door-to-needle time and cost savings. Fifty-four patients were included in this analysis; 26 received alteplase and 28 received tenecteplase. Door-to-needle time decreased from 56 minutes with alteplase to 36 minutes with tenecteplase, and over $50,000 was saved in 6 months by switching to tenecteplase. Additionally, door-in-door-out time decreased from 124 minutes with alteplase to 62 minutes with tenecteplase. This evaluation demonstrated that substituting tenecteplase for alteplase for treating acute ischemic stroke improves door-to-needle times and is a cost-effective alternative.
An ischemic stroke is the most common type of stroke that occurs when the brain’s blood vessels become narrowed or blocked, ultimately leading to severely reduced blood flow to the brain. When blood flow to the brain is interrupted, it deprives the brain of the oxygen and nutrients that it needs and leads to death of brain cells within minutes.1 For this reason, it is essential to restore blood flow to the ischemic areas of the brain as quickly as possible.
Alteplase is currently the only fibrinolytic agent FDA-approved for acute ischemic stroke. The dosing is 0.9 mg/kg (max 90 mg), with 10% of the dose given as an IV bolus over 1 minute and 90% of the dose given as a continuous infusion over 1 hour. There is strong evidence suggesting that IV tenecteplase has similar safety and efficacy outcomes compared with alteplase for the treatment of acute ischemic stroke.2-6 Tenecteplase is a variant of alteplase with a few structural modifications that results in increased fibrin specificity and a longer half-life, allowing for the convenience of a single bolus administration (0.25 mg/kg administered over 5 seconds; maximum dose 25 mg for the treatment of acute ischemic stroke).7,8 Additionally, tenecteplase currently costs significantly less than alteplase. Although tenecteplase is not currently FDA approved for the treatment of acute ischemic stroke, the American Heart Association 2019 updates to the Guidelines for Early Management of Acute Ischemic Stroke recommend considering the use of tenecteplase over alteplase.9
CHI Memorial Hospital began using tenecteplase as the exclusive IV thrombolytic for the management of acute ischemic stroke in July 2021. The goal of this evaluation is to assess the safety, time, and cost savings associated with using tenecteplase for the management of acute ischemic stroke compared with alteplase at CHI Memorial Hospital.
Methods
Evaluation Design and Patient Selection
This was a single-center, retrospective chart review. It was completed at CHI Memorial Hospital, a 423-bed community-based hospital composed of three campuses in Tennessee and Georgia: Chattanooga, Hixson, and Georgia. CHI Memorial is part of the Southeast Division of CommonSpirit Health, one of the nation’s largest nonprofit health systems with over 140 hospitals. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of an acute ischemic stroke, and received either alteplase or tenecteplase. Patients were excluded if they had a known history of drug allergy to either alteplase or tenecteplase. This evaluation was granted approval via a waiver of consent by the CommonSpirit Health Research Institute Institutional Review Board.
Data Collection and Statistical Analysis
Data were collected from the electronic health record (EHR) for patients who received either alteplase or tenecteplase for the treatment of an acute ischemic stroke in 2021. Six months of alteplase data (January 2021-June 2021) were compared with 6 months of tenecteplase data (July 2021-December 2021). Categorical data were assessed using Fisher’s exact test, while continuous data were assessed using Mann-Whitney U test. An alpha level of 0.05 was used for statistical significance.
Outcome Measures
The primary endpoints in this evaluation were median door-to-needle time and cost savings. Door-to-needle time was defined as time between patient arrival to the emergency department (ED) and administration of the thrombolytic. Secondary endpoints assessed included median door-in-door-out time, median door-to-needle time with a pharmacist present, median length of stay, number of overall post-thrombolytic intracranial hemorrhages (ICH), number of post-thrombolytic symptomatic ICH, and number of hypersensitivity and/or anaphylactic reactions. Door-in-door-out time was defined as time between patient arrival to the ED and patient transfer to an outside facility for mechanical thrombectomy of a large-vessel occlusion. In-house stroke alerts were excluded from the following analyses: door-to-needle time, door-in-door-out time, and length of stay.
Results
Baseline Characteristics
Fifty-four patients were included in this evaluation; 26 received alteplase and 28 received tenecteplase. Baseline characteristics were similar between groups (see TABLE 1). The median age was 67.5 years in the alteplase group and 74 years in the tenecteplase group. Baseline National Institutes of Health Stroke Scale (NIHSS) was 4.5 in the alteplase group and 5 in the tenecteplase group. The baseline Modified Rankin Scale score (mRS) was 0 in both groups. Of those who received alteplase, four had a large-vessel occlusion. In the tenecteplase group, five patients had a large-vessel occlusion. The only statistically significant difference seen in baseline characteristics was gender: 65.4% of the patients in the alteplase group were female; however, only 28.6% in the tenecteplase group were females (P = .01).
Primary and Secondary Outcomes
Overall, the median door-to-needle time decreased from 56 minutes with alteplase to 36 minutes with tenecteplase (P = .004). Median door-to-needle time was lower at the Chattanooga campus, with 52 minutes seen with alteplase and 32 minutes with tenecteplase (P = .005). The Hixson campus decreased from 57 minutes with alteplase to 35 minutes with tenecteplase (P = .273). Lastly, the Georgia campus decreased from 86 minutes with alteplase to 55 minutes with tenecteplase (P = .655). Approximately $50,000 was saved in 6 months by switching to tenecteplase. Additionally, median door-in-door-out time decreased from 124 minutes with alteplase to 62 minutes with tenecteplase (P = .03).
Pharmacist presence at stroke alerts on the Chattanooga campus helped decrease the door-to-needle time from 52 minutes to 44 minutes for alteplase administration and from 32 minutes to 31 minutes for tenecteplase administration. However, this was not found to be statistically significant. There were two post-thrombolytic ICH, both symptomatic, in the tenecteplase group (P = .49). The remaining secondary outcomes were similar between groups, including length of stay and number of hypersensitivity and/or anaphylactic reactions (see TABLE 2).
Discussion
In this retrospective chart review, significant improvement in door-to-needle times was realized by switching from alteplase to tenecteplase for the treatment of acute ischemic stroke (see FIGURE 1). Although the Hixson and Georgia campuses experienced improvements in their door-to-needle times, this was not considered to be statistically significant, presumably due to the smaller sample size at these campuses (see TABLE 3). Although it was not statistically significant, a pharmacist’s presence at a code stroke did improve door-to-needle times. A greater reduction in time was seen with alteplase; however, this is expected due to the ease of mixing and administration of tenecteplase compared with alteplase. Pharmacist documentation in the EHR was the sole marker to determine if they were present at the time of IV thrombolytic administration. Across both treatment groups, on average, pharmacists were only present at 45% of the stroke alerts. However, lack of documentation may play a role in this finding. It is the responsibility of the ED pharmacist to respond to code strokes. It is also important to note that pharmacists staff the ED only at the Chattanooga campus from 12 PM to 10 PM. There is no ED pharmacist staff coverage at the Hixson or Georgia campuses.
In addition to improved door-to-needle times, switching from alteplase to tenecteplase for the treatment of acute ischemic stroke decreased door-in-door-out time by 50%. There was a slight increase in ICH in patients who received tenecteplase. Although it was established to not be statistically significant, the clinical significance of that cannot be determined due to the low sample size of this review.
The results of this evaluation demonstrated that tenecteplase is a more cost-effective alternative. A 100 mg vial of alteplase costs CHI Memorial 31% more than a 50 mg vial of tenecteplase. By switching to tenecteplase, there was a cost savings of over $50,000 in a 6 month period (projected annual savings of over $100,000). Of note, in April 2022, the price of tenecteplase increased by 3% per 50 mg vial. However, this change was not reflected in the savings calculations as the price increased after the data had been analyzed.
There were some limitations within this evaluation. First, this was a retrospective chart review. Additionally, data were limited to what was documented in the EHR. Lastly, there was a global decline in stroke volume due to the COVID-19 pandemic.10 This study initially attempted to evaluate the difference in 30-day mRS scores between alteplase and tenecteplase patients, but poor outpatient follow-up prevented accurate data collection and analysis.
Moving forward, education on the importance of prompt door-to-needle times will be provided at all campuses, particularly Hixson and Georgia. Additionally, a change in workflow responsibilities will be initiated to allow pharmacists to respond to code strokes prior to the start of the ED pharmacist’s shift. In the near future, the Chattanooga campus will begin performing mechanical thrombectomies 24 hours a day. As a direct result, stroke care will no longer be delayed by facilitating transport of patients with large-vessel occlusions to an outside facility for additional endovascular therapy.
Conclusion
CHI Memorial Hospital began using tenecteplase as the exclusive IV thrombolytic for the management of acute ischemic stroke in July 2021 following extensive review of the data supporting tenecteplase as a safe and efficacious alternative to alteplase. Tenecteplase has increased fibrin specificity and a longer half-life, which results in less potential for bleeding and the convenience of a single bolus administration. Simpler preparation requirements allow for faster drug administration, less potential for error in dosing, and a reduction in ED staff time and resources. Furthermore, the data within this evaluation demonstrated that substituting tenecteplase for alteplase for the treatment of acute ischemic stroke is a cost-effective alternative and improves door-to-needle times.
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