Thread by @MehboobKalaniMD

nejm.org/doi/full/10.10… #LastWeekOnNEJM We reviewed the ANNEXA-4 Trial @AHNtoday for #AHNIMRes This trial was conducted to show the effectiveness of Andexanet Alfa as a reversal agent for major bleeds caused by Factor Xa inhibitors @TKapetanos @NEJM @KaminskiMed @Rick_Pescatore

Andexanet alfa is a modified inactive form of human factor Xa designed to bind and sequester factor Xa inhibitor molecules, thereby rapidly reducing anti-factor Xa molecules and activity

#Limitations (#BigLoad): 1) nonrandomized to placebo or another reversal agent 2) unblinded 3) Median age of 77 4) patients variably excluded during the study, ie only ICP bleeds were accepted from July 2016 to August 2017 5) GCS <7 or recent planned surgery were excluded

Limitations Cont: 6) Efficacy analysis done on patients with confirm major bleeding and anti-factor Xa level >75 ng/mL. seems like an arbitrary number, and not reproducible in an ED setting. results would be different if 100 patients were included in the analysis #StatsMagic

#StudyConclusion showed that Andexanet Alfa achieved good to excellent hemostatic efficacy in 82%. Decrease in anti-factor Xa level did not correlate with efficacy. Andexanet Alfa achieved “hemostatic efficacy at 12 hours, as adjudicated according to the prespecified criteria.”

Final thoughts: Too many limitations, placing results into question. Anti-factor Xa levels increased after infusion, and likely increasing bleeding risk. this drug does not clear the medications. Too expensive, and other options available. high thrombosis rate of 10% #NotWorthIt

No changes in guidelines. We need a good randomized control trial before any guidelines or hospital stewardship committee can change their ways. @tkap
@KaminskiMed @Rick_Pescatore @NEJM @NEJMres360 @MedEdPGH @MedEdBot Penny for your thoughts...