Tenecteplase an Alternative to Alteplase for Stroke Thrombolysis During Pandemic

By Will Boggs MD

July 22, 2020

NEW YORK (Reuters Health) - Tenecteplase can be useful as an alternative to alteplase for stroke thrombolysis during the COVID-19 pandemic, according to an opinion piece.

Alteplase, the standard thrombolytic agent for acute stroke, requires a 1-hour infusion and a dedicated second intravenous catheter, whereas tenecteplase is given as a single, 5-second intravenous bolus that requires about 2 minutes to mix, prepare, and administer. Moreover, alteplase is being used off label to treat acute respiratory distress syndrome associated with COVID-19, leading to supply shortages of the drug.

"In regions where there are prolonged surges of COVID-19 hospitalizations, emergency department and ICU nurses and physicians are repeatedly getting high-risk exposures to COVID-19 infected or suspected patients," Dr. Steven J. Warach from Dell Medical School, University of Texas and Ascension Texas, both in Austin, told Reuters Health by email. "Tenecteplase offers the possibility to reduce the intensity and duration of that exposure, without compromising stroke clinical outcomes."

Dr. Warach and Dr. Jeffrey L. Saver from Geffen School of Medicine at UCLA, Los Angeles, California describe these and other reasons for using tenecteplase as an alternative to alteplase and suggest ways of easing the transition between the two in their viewpoint article in JAMA Neurology.

Randomized trials and meta-analyses on ischemic stroke have shown tenecteplase to be noninferior to alteplase in this setting and possibly even superior for early recanalization. Although it is recommended as an alternative to alteplase in the most recent American Heart Association/American Stroke Association guidelines, tenecteplase is not approved by the U.S. Food and Drug Administration (FDA) for use in stroke.

In making the transition from alteplase to tenecteplase, hospitals need to achieve consensus within and across key clinical and administrative stakeholder and oversight groups. In some cases, hospitals will have to add tenecteplase to the hospital formulary.

In order to minimize the risk of error in selection and preparation of thrombolytic drug and dosage, the authors recommend implementation of one drug (tenecteplase) at one dosage (0.25 mg/kg) as the default option in the emergency department electronic medication-dispensing systems and the order set in the electronic health record.

Education of nurses and physicians should emphasize that only the drug and dosage are different. There are no changes to thrombolytic eligibility criteria or posttreatment monitoring. Clinicians also need to understand that the dose for stroke differs from that for acute myocardial infarction, so they should use the default dosage rather than the dosage information in the tenecteplase kit, which describes the acute myocardial infarction dosage.

Hospitals should replace alteplase with tenecteplase in the electronic health record ordering and monitoring tools and should keep a clinical registry of tenecteplase stroke cases so the data can be compared with prior alteplase experience.

"Additional randomized trials are in progress comparing alteplase and tenecteplase to prospectively test either noninferiority or superiority, and many centers have preferred to wait to see the results of those trials before switching," Dr. Warach said. "A switch to tenecteplase as the preferred stroke thrombolytic during the pandemic might be only a temporary measure for those centers that would not otherwise consider it an acceptable first-line stroke thrombolytic."

Dr. Deepak L. Bhatt from Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, whose meta-analysis of randomized clinical trials found thrombolysis with tenecteplase to be at least as effective and safe as thrombolysis with alteplase in acute ischemic stroke, told Reuters Health by email, "For stroke patients, it would greatly simplify care if there was one lytic at one dose. While they wrote this piece with COVID-19 in mind, the points they raise make sense even in non-pandemic settings."

"Scientifically, I don't see a downside to implementing their recommendations, though some physicians may be bothered due to guideline or FDA-labeling considerations," he said.

"Physicians (and health care systems) should use the COVID-19 pandemic to find ways to improve care, streamline processes, and reduce cost," Dr. Bhatt said. "And whatever lessons are learned should be applied to life post-pandemic. The authors have done a nice job of identifying such an opportunity."

Dr. Kameshwar Prasad from All India Institute of Medical Sciences, New Delhi, India, who emphasized the benefits of tenecteplase in acute ischemic stroke in his recent systematic review and meta-analysis, told Reuters Health by email, "Advantages of tenecteplase over alteplase include 3 Cs: Cost, Convenience, and now COVID-19. Tenecteplase has always had the first two, but COVID-19 has added a third one: less contact time and risk of transmission of COVID. Off-label use of tenecteplase instead of alteplase is justified."

"Cost issues deprive many poor uninsured patients of thrombolysis," he said. "Tenecteplase is one-third to one-fourth the cost of alteplase here."

"I think there is a need to think why there has been undue delay in companies generating adequate evidence to seek and obtain regulatory approval for tenecteplase" for ischemic stroke, Dr. Prasad added. "The probable reason is that research agenda is set not on the basis of public health need, but by the profit considerations of the pharma companies. An international body with adequate representation from all stakeholders should be set up to set global research agenda."

SOURCE: https://bit.ly/3jsc4YL JAMA Neurology, online July 20, 2020.

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