1a) Welcome to a two-part (today and Monday) live-tweeted, #accredited #tweetorial on 2⃣ 🔑#LBCTs from @ACCinTouch #ACC23 in #NewOrleans 🥳on advances in #hyperlipidemia management #LLT. Our expert presenter and commentator is none other than @CMichaelGibson. pic.twitter.com/5BflV3bKka
— cardio-met (@cardiomet_CE) March 4, 2023
2) This program is supported by an educational grant from Esperion Therapeutics & is intended for #HCPs. Statement of accreditation & faculty disclosures at https://t.co/gvXca4G9Xm. Earn 0.75 hr 🆓CE/#CME by following this 🧵and completing the form posted with Part 2.
— cardio-met (@cardiomet_CE) March 4, 2023
4a) Cardiovascular disease (#CVD) is #1 cause of ☠️in 🇺🇸 & 🇪🇺. #Dyslipidemia is one of the primary causal factors in development of #atherosclerotic CVD (#ASCVD), guidelines rec tx of dyslipidemia for both primary & secondary prevention of ASCVD. pic.twitter.com/UhbPei11T5
— cardio-met (@cardiomet_CE) March 4, 2023
4c) Alternative & new drug classes have demonstrated further #CV event reduction when subbed for or added to #statins. See https://t.co/fC7MS6JsfF for more 🆓CE/#CME on @nationallipid guidance on these drugs, found at 🔓https://t.co/GTHrtveS8v. pic.twitter.com/2orOh871hl
— cardio-met (@cardiomet_CE) March 4, 2023
5) So . . . #CLEAR_OUTCOMES #LBCT at #ACC23, presented by Steven Nissen. This trial is testing the hypothesis that administration of #bempedoic_acid, added to standard medical tx, will ⬇️risk for #CV events in pts w/ high vascular risk ➕statin intolerance. pic.twitter.com/kwIrtuPznH
— cardio-met (@cardiomet_CE) March 4, 2023
7) The #bempedoic_acid label authorizes tx of established #ASCVD in pts who require additional LDL-C ⤵️ing after max tolerated statin therapy, and in treatment of heterozygous familial #hypercholesterolemia (#HeFH). It may be given as an adjunct to statins &/or other tx.
— cardio-met (@cardiomet_CE) March 4, 2023
9) #CLEAR_OUTCOMES was an event-driven study with a primary #outcome of a composite of ⌛️ to first #CV death or first nonfatal #MI, nonfatal #stroke, or #coronary_revascularization. Here are the characteristics of the enrolled pts: pic.twitter.com/bfzaytzG1e
— cardio-met (@cardiomet_CE) March 4, 2023
11a) So let’s think mechanism of action: #bempedoic_acid is an ATP citrate lyase inhibitor ➡️ ⬇️ hepatic cholesterol synthesis upstream of #HMG_Co_A_reductase, the enzyme inhibited by #statins.
— cardio-met (@cardiomet_CE) March 4, 2023
11c) So versus placebo? Quite well . . . whether assessed specifically by extent of ⤵️#LDL_C, or by the broader anti-inflammatory measure of ⤵️#hs_CRP: pic.twitter.com/VoFKLv5KCm
— cardio-met (@cardiomet_CE) March 4, 2023
13a) Efficacy outcomes, #bempedoic_acid vs placebo, 70% secondary prevention:
— cardio-met (@cardiomet_CE) March 4, 2023
🫀 13% significant ⬇️in 4⃣-component #MACE
🫀 15% significant ⬇️in 3⃣-component MACE
🫀 23% significant ⬇️in fatal/nonfatal MI
🫀 19% significant ⬇️in #coronary #revasc
14) By way of comparison, these efficacy data next to other non-statin therapies are right in line, but keep in mind #bempedoci_acid is an oral agent 💊: pic.twitter.com/rAT2nqB9fj
— cardio-met (@cardiomet_CE) March 4, 2023
16) An early look at subgroup analysis for the #MACE-4 endpoint offers a reflection over the overall trial data, including ♀️ patients–with 4⃣8⃣ % females, #CLEAR_OUTCOMES offers a new benchmark for assessing ♀️🫀 care! pic.twitter.com/KtztT02ImX
— cardio-met (@cardiomet_CE) March 4, 2023
18) The authors’ conclusions, which are also included in a simultaneous publication in @NEJM: pic.twitter.com/r5zKrR75yS
— cardio-met (@cardiomet_CE) March 4, 2023
19b)
— cardio-met (@cardiomet_CE) March 4, 2023
♀️🫀 these are 🔑data for improving outcomes in heart dz in women, who more often have statin intolerance than men
See https://t.co/xie61As1KB pic.twitter.com/HSc7o7gLJD
21) Welcome back to our focused review of #LBCT data on #LLT from #ACC23! Scroll ⤴️for a review by our esteemed faculty @CMichaelGibson of the Ph 3⃣ #CLEAR_OUTCOMES data, now published at https://t.co/OG2ntak2Ce.
— cardio-met (@cardiomet_CE) March 6, 2023
23) The drug is #MK_0616, an investigational macrocyclic peptide that binds to #PCSK9 & inhibits the interaction of PCSK9 with LDL receptors. As with #parenteral PCSK9i, this ➡️ ⬆️ numbers of #LDL receptors available on the cell surface to remove LDL cholesterol from the blood.
— cardio-met (@cardiomet_CE) March 6, 2023
25) Today's #ACC23 #LBCT presentation is highlighted here in real time! pic.twitter.com/ndRePt634m
— cardio-met (@cardiomet_CE) March 6, 2023
27) #MK_0616 has a clear mechanism of action with with monoclonal antibody-like affinity to #PCSK9. pic.twitter.com/3u81UokilI
— cardio-met (@cardiomet_CE) March 6, 2023
29) The primary objective of the study is to evaluate the effect of #MK_0616 🆚 placebo on % change from baseline in #LDL_C at 8 wks, with the hypothesis that at least one of the studied doses would meet that objective with acceptable safety.
— cardio-met (@cardiomet_CE) March 6, 2023
30b) . . . and baseline characteristics of the patients enrolled are shown here. Note that half the patients are ♀️, 55% have #diabetes, and nearly 2/5 already have clinical #ASCVD. pic.twitter.com/ve5BFXgjr9
— cardio-met (@cardiomet_CE) March 6, 2023
32) The primary #EP was met by all 4⃣ doses, with limited dose-dependency at the 12mg dose and ⬆️ and was reached by 2 weeks, without substantial dose-related issues with safety 🛟 and tolerability🤮🤢: pic.twitter.com/vHmlqoIqwT
— cardio-met (@cardiomet_CE) March 6, 2023
34) @CBallantyneMD's summary: pic.twitter.com/DCS1EFUyxj
— cardio-met (@cardiomet_CE) March 6, 2023
35b)
— cardio-met (@cardiomet_CE) March 6, 2023
🫀 Tho the numbers of #AEs are small, we need more detail.
🫀 A larger study with broader inclusion criteria is certainly warranted.
🥳to @CBallantyneMD et al on this study and simultaneous publication in #JACC! pic.twitter.com/5R2RKe747h
37) What is the mechanism of action for #bempedoic_acid?
— cardio-met (@cardiomet_CE) March 6, 2023
a. inhibits HMG-CoA reductase
b. inhibits ACLY
c. prevents GI absorption of lipids
d. increased # of LDL-C receptors
39) What is the mechanism of action for #PCSK9 inhibitors?
— cardio-met (@cardiomet_CE) March 6, 2023
a. reduces the degradation of LDL receptors
b. increases the clearance of LDL cholesterol.
c. prevents GI absorption of lipids
d. a & b
40b) And D on 39, right? If not, go to @PamTaubMD's https://t.co/1WTBo2NPhT and earn EVEN MORE CE/#CME! Now you see why following @cardiomet_ce is the right thing to do!
— cardio-met (@cardiomet_CE) March 6, 2023
41) Right now you can go to https://t.co/XdayA7OAR3 and earn 0.75hr CE/#CME for completing this program of two "real-time" tweetorials! @CMichaelGibson and @academiccme thank you for joining us!
— cardio-met (@cardiomet_CE) March 6, 2023