Join the NCS Pharmacy Section on Monday, April 6 at 1 PM CT for this month's journal club and chat with colleagues on social with #NCSPharmJC. Log in to your NCS account and visit the Pharmacy Section: connect.neurocriticalcare.org/home/memberhome
Join the NCS Pharmacy Section on Monday, April 6 at 1 PM CT for this month's journal club and chat with colleagues on social with #NCSPharmJC. Log in to your NCS account and visit the Pharmacy Section: connect.neurocriticalcare.org/home/memberhome
Dr. Daniel's takeaway: Argatroban and eptifibatide, when used as adjunctive therapies to IV thrombolytics, did not reduce disability and may be associated with harm.
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Dr. Daniel's takeaway? The response adaptive design was robust and allowed for trial flexibility and was both strengthened and limited by the exclusive eligibility of patients who received thrombolysis and IAT
Overall, MOST shows adjunctive AC/AP does not improve outcomes
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The authors conclude that in patients with AIS treated with IV thrombolytics within 3 hours of symptom onset, adjunctive treatment with IV argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality
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Looking at more "traditional" figures, you can see that the likelihood of achieving a traditional mRS of 0-2 was lower with argatroban and there was no benefit with revascularization
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The posterior probability of argatroban and eptifibatide being superior to placebo was 0.002 and 0.041, respectively
Rates of bleeding were higher with argatroban especially compared to placebo
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About 500 patients were enrolled with the argatroban group stopping early due to a signal of harm
The trial was ultimately stopped early due to the futility criteria being met
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The trial was a triple-arm, adaptive RCT that aimed to assess the uw-mRS at 90 days between arms and included key safety outcomes
Argatroban was given as a 100 mcg/kg bolus followed by 3 mcg/kg/min x12h
Eptifibatide was started at a 135 mcg/kg bolus followed by 0.75 mcg/kg/min x2h
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Given the gaps in the evidence, the MOST trial aimed to evaluate the comparative effectiveness and safety of adjunctive intravenous argatroban or eptifibatide in patients with ischemic stroke treated with intravenous thrombolytics in pts who received tPA within 3h of LKW
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This is not the first time these agents have been investigated - Dr. Daniel explores the prior trials exploring adjunctive argatroban and eptifibatide
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Dr. Halimanovic's summary: The TRACE III trial demonstrated that in areas lacking thrombectomy resources, administering tenecteplase within 24 hours of stroke onset may improve outcomes for patients with large-vessel occlusion.
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How can we extend the effectiveness of thrombolysis? Argatroban and eptifibatide may adjunctively improve arterial thrombus dissolution by affecting a different location of the clotting cascade
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Next up: Morgan Daniel, PharmD, PGY2 neurology resident at Grady Health presents the MOST trial evaluating adjunctive argatroban or eptifibatide for ischemic stroke
How can we extend the effectiveness of thrombolytics after AIS? MOST aimed to assess this!
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What was a key finding of the TRACE-III trial regarding the use of TNK in patients with ischemic stroke?
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What is Dr. Halimanovic's takeaway?
TRACE III was well-designed but is notably limited by the selection of only patients who did not have access to thrombectomy
The trial suggests extended window TNK could be reasonable in some patients, but more generalizable evidence is needed
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The study aimed to assess the rate of mRS 0-1 at 90 days between arms and described major safety outcomes as well
Over 500 patients were randomized and were relatively representative of a standard stroke population (of note all in China)
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TRACE III aimed to investigate the efficacy of TNK 4.5-24 hours after stroke with LVO who did NOT have access to thrombectomy and had salvageable tissue, randomizing patients to TNK 0.25 mg/kg to SOC
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One way to approach these limitations is to extend the traditional window for thrombolysis - but what is the data for this? Dr. Halimanovic reviews the EXTEND and TIMELESS trials which provide the basis for this trial
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First up on #NCSPharmJC: Medina Halimanovic, PharmD, PGY2 CC resident an IU Health is presenting the TRACE III trial on TNK up to 24 hours after AIS with LVO without thrombectomy
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Starting shortly! Follow along for major takeaways and key points from the presentations. #NCSPharmJC
If you have any questions or discussion points, feel free to reply and I will ask the presenters on the JC!
Join us for the @neurocritical.bsky.social November Pharmacy Journal Club TOMORROW, 11/22 at 2pm EST! DM me for Zoom information or find it on the NCS Pharmacy Connect page.
Two excellent articles on AIS care - TRACE III and MOST - will be presented!
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