2) Yes, #ChristianRuffMD just left the podium and we have MUCH to discuss in this LIVE program from #AHA23. Our guest author is Sid Patel MD @SidPatelMD, #Cardiology & #CriticalCare @BrighamFellows @HarvardMed & Research Fellow @TIMIStudyGroup. pic.twitter.com/JqWP0jWqGb
— cardio-met (@cardiomet_CE) November 12, 2023
4) We've known for DECADES that #anticoagulation can ⬇️ reduce #stroke risk in pts w/ #AFib by >60%. Those data of course came from use of #VKAs, but were encumbered by numerous problems w/ VKAs, esp need for monitoring, XS 🩸, and #DDIs.
— cardio-met (@cardiomet_CE) November 12, 2023
6a) But hey–(we hope) medicine always moves forward, right? Now in 2023 it requires only a curbside consult with Dr Google to show cracks in the facade with DOACS in the #AFib patient. Only a FEW examples: pic.twitter.com/BensamXJIE
— cardio-met (@cardiomet_CE) November 12, 2023
6c) Concern for greater bleeding risk particularly in the setting of #CKD:
— cardio-met (@cardiomet_CE) November 12, 2023
🔓 https://t.co/UHeTXHx87q pic.twitter.com/92bfHMkAjM
6e) Drug-drug interactions #DDIs–not as many concerns as with #VKAs, but still a problem!
— cardio-met (@cardiomet_CE) November 12, 2023
🔓 https://t.co/uAnO9lXWOy
🔓https://t.co/beVfB045uW
OK–your library has now been adequately supplemented. So there is still room for improvement—but HOW?
7b) This allows us to see a potential way to "divide and conquer" this process UPSTREAM of the common pathway: by specifically inhibiting (only) #FXI: pic.twitter.com/Ygl1W2r24p
— cardio-met (@cardiomet_CE) November 12, 2023
8b) It's C. With the new "vision" of the coagulation cascade, specific inhibition of FXI has the potential to reduce pathologic thrombosis without overtly increasing bleeding risk.
— cardio-met (@cardiomet_CE) November 12, 2023
9b) Other #FXI inhibitors are also under investigation
— cardio-met (@cardiomet_CE) November 12, 2023
👉#asundexian vs apixaban (#OCEANIC_AF, NCT05643573)
👉#milvexian vs apixaban (#LIBREXIA_AF, NCT 05757869)
emphasizing need for safe and reliable #anticoagulation in the burgeoning #AF population worldwide.
10) And so #AZALEA #TIMI-71 is testing the promise of greater safety with #FXI inhibition vs. a routinely used #DOAC in clinical practice, #rivaroxaban.
— cardio-met (@cardiomet_CE) November 12, 2023
12) We summarized this all for you in https://t.co/JLnQl6N5cH. But now, #AHA23 has arrived, and we have the data behind the #DMC action. It's #LBCT time–and YOU ARE THERE! pic.twitter.com/RcUMkaHtfe
— cardio-met (@cardiomet_CE) November 12, 2023
14) You read about the design of the Ph 2 #AZALEA_TIMI-71 study in posts 9c and 10. The purpose of the study was to evaluate the bleeding profile of #abelacimab relative to #rivaroxaban in patients with #AF at moderate-to-high risk of #stroke, with that risk defined as: pic.twitter.com/azBmAnjUZm
— cardio-met (@cardiomet_CE) November 12, 2023
16a) Those patients randomized to #abelacimab 150mg SQ q month demonstrated full (ie., ~99%!) inhibition of Factor XI, essentially mimicking congenital factor XI deficiency with consistency (IQR 98-99%) pic.twitter.com/IJqTwDcfMu
— cardio-met (@cardiomet_CE) November 12, 2023
17) Glad you asked! The primary EP of #AZALEA was major or clinically relevant non-major bleeding #CRNMB. And here are the data, showing the dramatic reduction in 🩸EPs, including almost complete elimination of GI 🩸 – the Achilles heel of the #DOACs. pic.twitter.com/x2xPMDRRUq
— cardio-met (@cardiomet_CE) November 12, 2023
18b) . . . leading the trial's independent #DMC to issue this noteworthy recommendation: pic.twitter.com/TN9zSfG7WD
— cardio-met (@cardiomet_CE) November 12, 2023
19b) A dedicated, larger phase 3 trial (#LILAC-TIMI 76) is ongoing to examine the efficacy of #abelacimab in stroke prevention for #AF.
— cardio-met (@cardiomet_CE) November 12, 2023
21a) So in the largest trial of FXI inhibition with the longest follow-up reported to date, #abelacimab substantially reduced bleeding vs #rivaroxaban, providing support of #FXI inhibition as a safer target for anticoagulation in #AF. pic.twitter.com/IseZAW5nbb
— cardio-met (@cardiomet_CE) November 12, 2023
22) And again, efficacy will be addressed in a #placebo-controlled trial called #LILAC_TIMI-76 (NCT05712200). The #FXI hypothesis is also being tested with #milvexian and #asundexian in other ongoing trials. Exciting stuff! pic.twitter.com/I1YXuOqDuR
— cardio-met (@cardiomet_CE) November 12, 2023
24a) So, in #AZALEA_TIMI-71, #abelacimabinhibited #FXI by
— cardio-met (@cardiomet_CE) November 12, 2023
25a) In AZALEA, which of the following is true regarding #abelacimab vs #rivaroxaban?
— cardio-met (@cardiomet_CE) November 12, 2023
a. Similar bleeding of all types
b. ⬇️ #ICH but similar major bleeding
c. ⬇️ major & #CRNMB, but ⬆️ #GIbleeding
d. ⬇️ major, clinically relevant non-major, & gastrointestinal bleeding
26) And it's as if you were right here at #AHA23. @SidPatelMD has made sure you got all the 🆕 data, and @cardiomet_ce makes sure now you get 0.5hr 🆓CE/#CME. Claim your certificate at https://t.co/BmdD71HDA2. Thank you for joining us! Follow us for the best #MedEd on X!
— cardio-met (@cardiomet_CE) November 12, 2023