2) The expert faculty for this session were @ShaunGoodman, @connors_md, @MellanieHills of @stopafib, & the inimitable #JeffWeitzMD. Learning from this #tweetorial can earn you an extra 0.5hr 🆓CE/#CME!
— cardio-met (@cardiomet_CE) July 12, 2023
Faculty disclosures & statement of accreditation at https://t.co/gvXca4G9Xm pic.twitter.com/qbqSdTG3w1
4) There is of course much excitement about the potential of specifically impairing #FXI / #FXIa & the #intrinsic #coagulation pathway as a means of allowing safe ⬆️ in the magnitude of #anticoagulation without sustaining a corresponding ⬆️ in the extent of bleeding risk. pic.twitter.com/IsbUyBsgAk
— cardio-met (@cardiomet_CE) July 12, 2023
6a) Despite well-documented advances in #anticoagulation tx (#warfarin➡️#DOACs; #UFH➡️ #LMWH➡️DOACs; #UFH➡️#DTIs, etc), there remain unmet needs, to wit:
— cardio-met (@cardiomet_CE) July 12, 2023
1⃣ #thrombosis ➡️1 in 4 🪦 globally
2⃣ #DOACs are safer than warfarin (esp re #ICH) but major/fatal bleeds still occur
(cont) pic.twitter.com/ufewjMd29Z
6c)
— cardio-met (@cardiomet_CE) July 12, 2023
5⃣ Other limitations of #DOACs
–Relatively short half-life requires once/twice daily adherence/persistence
–Drug-drug interactions
–Dependent on renal clearance to some extent
–DOAC dose adjustment may be inappropriate pic.twitter.com/44X4pq2H2a
8) Yet treatment patterns in the 🇺🇸 indicate that providers are not meeting the challenge. See prior tweetorials at https://t.co/orYQvmXHu9 & https://t.co/LmVfYMNLuZ (and still earn 🆓 CE/#CME) that explore issues with both #underprescribing & poor adherence. pic.twitter.com/XUvQ7inIJk
— cardio-met (@cardiomet_CE) July 12, 2023
9b) … and the last of these is perhaps the most dangerous and disconcerting, because subtherapeutic doses of #OACs both DON'T provide adequate #stroke protection and DON’T decrease risk of #hemorrhage! pic.twitter.com/4ie9ZpFceQ
— cardio-met (@cardiomet_CE) July 12, 2023
11a) Why do patients miss a dose of their #DOAC? Could be an inadvertent consequence of pill burden 💊💊💊, which is common in pts with #AFib, especially older individuals . . . and in and of itself impacts quality of life #QoL! pic.twitter.com/1vQuPepm3W
— cardio-met (@cardiomet_CE) July 12, 2023
12a) Beyond #pillburden, patients may well skip a dose on purpose . . . in response to what we clinicians tend to call "nuisance #bleeding". In this @isth symposium it was suggested we refer to it more appropriately as "patient-relevant bleeding." Here are some reasons why: pic.twitter.com/vI1gAysf8J
— cardio-met (@cardiomet_CE) July 12, 2023
13a) So what potential new approaches are there? Which of the following appears to be the best target for novel anticoagulant strategies?
— cardio-met (@cardiomet_CE) July 12, 2023
13c) Well, what if we could #uncouple the intersecting processes of (physiologic) #hemostasis & (pathologic) #thrombosis? This could happen if we were to specifically & solely impact the INTRINSIC pathway, either at #FXI or #FXII (NB so far anti-FXII approaches haven't worked).
— cardio-met (@cardiomet_CE) July 12, 2023
13e) 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/3YWwQrdOJv
— cardio-met (@cardiomet_CE) July 12, 2023
13g) It’s c, Factor XII and #thrombin. That feedback loop whereby thrombin activates #FXI to #FXIa is a key reason why FXI inhibition is potentially so effective at blocking pathological #thrombosis.
— cardio-met (@cardiomet_CE) July 12, 2023
14b) Note that only #abelacimab, one of the monoclonal antibodies #MAb (it’s fully humanized) being studied, inhibits both #FXI and #FXIa. While the clinical significance of this ability is still being evaluated, mechanistically it means that abelacimab not only prevents . . .
— cardio-met (@cardiomet_CE) July 12, 2023
15a) Because of the limited effect on hemostasis, selective #FXI inhibition is now being studied in multiple Ph 3 #AFib trials:
— cardio-met (@cardiomet_CE) July 12, 2023
🫀 #Abelacimab: LILAC-TIMI 76 (NCT05712200)
🫀 #Asundexian: OCEANIC-AF (NCT05643573)
🫀 #Milvexian: LIBREXIA-AF (NCT 05757869)
15c) #LILAC is different; prior to enrollment, all pts are untx'd for #SPAF (due to h/o bleeding, potential DDIs, or multiple comorbidities complicating conventional #anticoagulation) & are already “on placebo” by choice/decision. For half the subjects, “placebo” will continue.
— cardio-met (@cardiomet_CE) July 12, 2023
16b) #FXI-targeted #SPAF regimens, currently being evaluated in Ph 3 trials for three novel agents, offer great potential for an improved approach to #stroke reduction in these patients, as well as in other thrombotic diseases.
— cardio-met (@cardiomet_CE) July 12, 2023
17) So watch this space as data accrue! And RIGHT NOW you can grab 0.5hr 🆓CE/#CME just for having joined us here! Point your 🖱️ to https://t.co/JYtFH8kcHW and your certificate awaits you. FOLLOW US for more expert-led #cardiometabolic #MedEd delivered wholly on Twitter! pic.twitter.com/1prSgLwH0A
— cardio-met (@cardiomet_CE) July 12, 2023