2) Our returning expert faculty is Sid Patel MD @SidPatelMD #Cardiologist @HarvardMed @TIMIStudyGroup. Sid helped lead the #AZALEA trial and presented the first secondary analysis from it at #ESC2024, from which you can still earn CE/#CME at https://t.co/T6f0nRVJgb pic.twitter.com/8fkr2Rbecd
— cardio-met (@cardiomet_CE) November 16, 2024
3b) Which is FALSE about #FXI/XIa-targeted agents in development?
— cardio-met (@cardiomet_CE) November 16, 2024
a. multiple #MOAs are being tested
b. both FXI & FXIa are potential 🎯s
c. Pts on #OAPs are excluded from FXI/XIa #AF trials
d. a Ph 2 trial of a FXI inhibitor was stopped early for superior safety v a DOAC
4a) Use of #DOACs is indeed complicated to some extent by enzyme-related #DDIs with, e.g., #SSRIs & #SNRIs, but especially by a pt's need for con meds that ALSO ⬆️bleeding, such as #ASA, #OAPs, & #NSAIDs. An anticoagulant that reduces bleeding might be easier to use.
— cardio-met (@cardiomet_CE) November 16, 2024
5) If we were to specifically & solely impact the INTRINSIC pathway, either at #FXI or #FXII (NB so far anti-FXII approaches haven't worked), we could #uncouple the intersecting processes of (physiologic) #hemostasis & (pathologic) #thrombosis.
— cardio-met (@cardiomet_CE) November 16, 2024
7) 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/HAGsjG2h19
— cardio-met (@cardiomet_CE) November 16, 2024
8b) New approaches for #stroke ⬇️ in #AFib have been #MAb against #FXI and small molecule inhibitors of #FXIa. Leading candidate from each of these categories currently in Ph 3 trials: MAb #abelacimab in #LILAC #TIMI-76 & small molec #milvexian in #LIBREXIA_AF.
— cardio-met (@cardiomet_CE) November 16, 2024
10) So @SidPatelMD was in the room here at #AHA24 for @cardiomet_CE as @TIMIStudyGroup #fellow Samer Al Said @sameralsaid presented a second preplanned analysis from #AZALEA TIMI_71, looking at concomitant use of #OAPs with either #abelacimab or #rivaroxaban. pic.twitter.com/Og8uj9eDBC
— cardio-met (@cardiomet_CE) November 16, 2024
12) This trial was terminated prematurely due to a substantial reduction in bleeding with #abelacimab as per the independent #DMC statement: pic.twitter.com/GJrATbQ0ii
— cardio-met (@cardiomet_CE) November 16, 2024
14) This dramatic reduction in bleeding occurred despite robust inhibition of #FXI, which at the 150mg monthly dose (the dose carried forward, BTW, into #LILAC #TIMI-76) was associated with near-total inhibition: pic.twitter.com/eWkdkXBd6S
— cardio-met (@cardiomet_CE) November 16, 2024
16) Use of one of these agents was NOT an exclusion criterion in #AZALEA, but pts taking #OAPs on entry & randomization were prospectively tracked as a separate cohort of interest for 🩸complications. That was the subject of today's presentation. pic.twitter.com/SNphpuLZUJ
— cardio-met (@cardiomet_CE) November 16, 2024
17b) A particularly appealing potential of a #FXI/XIa-targeted #anticoagulant is the ⬇️ bleeding risk they seem to offer vs #DOACs. Might this translate to patients on concomitant #OAPs? pic.twitter.com/3ZcpdcPwsj
— cardio-met (@cardiomet_CE) November 16, 2024
19) The pts receiving #OAPs were, as would be expected, more likely to be male and more likely to have “hard” markers of #ASCVD—higher rates of prior diagnoses of #MI, #CAD, & #PAD. Keep in mind these pts ALL also had #AFib with mod-high risk of #stroke. pic.twitter.com/MUxNUutDfV
— cardio-met (@cardiomet_CE) November 16, 2024
20b) The interesting finding is that the addition of #OAP therapy to #anticoagulation created another differential between #rivaroxaban & #abelacimab: adding #OAP to riva significantly ⬆️ 🩸, but adding OAP to abelacimab did not! pic.twitter.com/d9X0rgNtzK
— cardio-met (@cardiomet_CE) November 16, 2024
22) The authors did note some limitations of this analysis, and pointed out that a Phase 3 study for efficacy AND safety of abelacimab is underway (#LILAC #TIMI-76, NCT05712200). pic.twitter.com/xvHdJUtv4m
— cardio-met (@cardiomet_CE) November 16, 2024
24) @sidpatel & the #TIMI investigators further commented that if shown to be effective for prevention of ischemic events in ongoing Ph 3 trials, FXI inhibitor tx may be esp attractive for pts requiring #OAP – a subset of patients typically at much higher risk for bleeding.
— cardio-met (@cardiomet_CE) November 16, 2024
25) Thank you for joining us for this update from #AHA2024! You may now proceed to https://t.co/iltVNqK021 and collect your 🆓CE/#CME certificate! Thanks as always to @SidPatel (and to @sameralsaid!) for leading us through these hot-off-the-presses data!
— cardio-met (@cardiomet_CE) November 16, 2024