1b) @ProfKausikRay will particularly focus on data for non-#statin #LLT from #ESCCongress, following on the heels of the presentation of the primary analysis of #CLEAR_Outcomes at #ACC23, about which you learned from @CMichaelGibson in our tweetorial at https://t.co/XdayA7OAR3.
— cardio-met (@cardiomet_CE) August 26, 2023
3) 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/nPPC45WAYX
— cardio-met (@cardiomet_CE) August 26, 2023
5a) Alternative & new drug classes have demonstrated further #CV event reduction when subbed for or added to #statins. #Ezetimibe in #EWTOPIA (https://t.co/xvpBNBZgr0) showed benefit w/o statins, but is generally rec’d as add-on only, similar to #PCSK9i.
— cardio-met (@cardiomet_CE) August 26, 2023
5b) This doc defines #statin_intolerance as adverse effect/s assoc'd w/statin tx that resolve/improve w/ dose ⤵️or d/c, classified as complete inability to tolerate any dose of statin, or partial intolerance w/ inability to tolerate necessary dose to achieve pt's tx objective. pic.twitter.com/VfIxZuMilu
— cardio-met (@cardiomet_CE) August 26, 2023
7) #CLEAR_Outcomes was a randomized, double-blind, placebo-controlled, event-driven trial. As a reminder, #bempedoic_acid was approved by @US_FDA in 2020 based on trial data ➡️⬇️ lower #LDL by 15–25% alone, & by up to 38% when combined with #ezetimibe.
— cardio-met (@cardiomet_CE) August 26, 2023
9a) Reminder re 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) August 26, 2023
10) Tolerance is good . . . but also the clinical readout from #CLEAR_Outcomes was positive for both biomarkers (⤵️#LDL_C, ⤵️#hs_CRP) and, more importantly, for clinical endpoints: pic.twitter.com/TNMdNbMU7t
— cardio-met (@cardiomet_CE) August 26, 2023
12a) The separate analysis of the 30% of #CLEAR_Outcomes patients who were enrolled for primary prevention was presented at #ADA23 and was covered there by our faculty @cpcannon. His tweetorial is still available for CE/#CME credit at https://t.co/03d7bb0AXb.
— cardio-met (@cardiomet_CE) August 26, 2023
12c) Outcomes in the #primaryprevention cohort were similar to those in #CLEAR_Outcomes overall, with clear efficacy for #bempedoic_acid over placebo, including for both #CV death and all-cause mortality ☠️: pic.twitter.com/F0NoJaApIO
— cardio-met (@cardiomet_CE) August 26, 2023
14) The authors' conclusions from #CLEAR_Outcomes were as follows:
— cardio-met (@cardiomet_CE) August 26, 2023
See also @NEJM https://t.co/OG2ntak2Ce pic.twitter.com/mp2rexm1bm
16a) This consideration is 🔑among #hyperlipidemic patients for many reasons:
— cardio-met (@cardiomet_CE) August 26, 2023
🫀 #diabetes, an ⬆️ingly prevalent disease globally, doubles the risk of #ASCVD
🫀 #LDL-C lowering with #statins as first-line treatment reduces this risk in patients with #DM (#CARDS trial)
16c) (cont)
— cardio-met (@cardiomet_CE) August 26, 2023
🫀 #Statins ⬆️risk of new-onset diabetes (#NOD) in a dose-dep fashion, but trials of #ezetimibe or #PCSK9i added to statins ➡️no excess risk of NOD
🫀 Genetic studies suggest that ⬇️activity of #ACLY (as per #bempedoic_acid MOA) would ⬇️CVD with no excess risk of #NOD
18) And what did we find? As we might expect, the incidence of #CV events in the placebo group ⬆️ across glycaemic strata, but at 6mos, ⬇️in LDL and non-HDL -C w/ #bempedoic acid were SIMILAR across those same strata: pic.twitter.com/vvnWLbrZwV
— cardio-met (@cardiomet_CE) August 26, 2023
20) . . . without worsening #HbA1c or glucose levels in those without #diabetes, without ⬆️ risk of #NOD, and with more weight loss compared with placebo: pic.twitter.com/GgSZKpLxrp
— cardio-met (@cardiomet_CE) August 26, 2023
22) But wait, there's more! The new #LLT data for #statin-intolerant patients just kept coming today at #ESCCongress #ESC23 @escardio, with another secondary analysis of #CLEAR_Outcomes in the same #LBCT session! pic.twitter.com/b6zjtIwcdj
— cardio-met (@cardiomet_CE) August 26, 2023
24a) While the association of ⬆️#LDL_C w/ long term #CV risk is well established, #CLEAR_Outcomes validated the utility of #bempedoic_acidto ⬇️1st #MACE events in high-risk pts w/ #statin intolerance & high LDL-C levels.
— cardio-met (@cardiomet_CE) August 26, 2023
25) Here's the #methodology & some baseline data. Keep in mind f/u in this trial was almost 3.5 years–long enough to capture these singular and multiple #CV events: pic.twitter.com/5wo2oSEJsE
— cardio-met (@cardiomet_CE) August 26, 2023
27) #Bempedoic_acid significantly reduced the incidence of both first and multiple events vs placebo, with significant benefits across the spectrum of #CV complications: reduced the total incidence of MACE-4 by 20%, MACE-3 by 17%, MI by 31%, & coronary revascularization by 22%. pic.twitter.com/lAUUBK4TCi
— cardio-met (@cardiomet_CE) August 26, 2023
29) The overall, significant benefit in ⬇️ #HR of increasing numbers of #CV events, and the risk difference that results, can be quantified in this novel analysis from #CLEAR_Outcomes: pic.twitter.com/hBzW38rW90
— cardio-met (@cardiomet_CE) August 26, 2023
30b) . . . but then presented these impactful conclusions: pic.twitter.com/i6W8WAq7gV
— cardio-met (@cardiomet_CE) August 26, 2023
32a) So let's review, and then you can claim your 🆓#MedEd credit!
— cardio-met (@cardiomet_CE) August 26, 2023
What is the mechanism of action of #bempedoic_acid as a #LLT?
a. inhibits HMG-CoA reductase
b. inhibits ATP Citrate lyase
c. prevents GI absorption of lipids
d. increased # of LDL-C receptors
33a) Now, across the glycaemic spectrum in #CLEAR_Outcomes, which of the following was NOT found with #bempedoic acid compared to placebo?
— cardio-met (@cardiomet_CE) August 26, 2023
a. higher incidence of #NOD
b. weight loss
c. improved #MACE3 outcomes
d. improved #MACE4 outcomes
34a) Finally, during 3.4 years f/u of 13,970 high-risk #hyperlipidemic #statin-intolerant pts, about 34% of pts had multiple CV events. Which of these was the most common "additional" event?
— cardio-met (@cardiomet_CE) August 26, 2023
a. nonfatal #MI
b. nonfatal #stroke
c. #CV death
d. #coronary #revascularization
35) Hopefully we were able to transport you to #Amsterdam & these 2 #LBCT presentations at #ESC23. Could you taste the edam & the gouda? Are you eager to get out on busy city streets on a 🚲? Before you leave, go to https://t.co/lcgSWzRVxu and grab your 0.75hr CE/#CME credit!
— cardio-met (@cardiomet_CE) August 26, 2023
36) And please join expert lipidologists @ProfKausikRay, @PamTaubMD, @CBallantyneMD, @DrMarthaGulati, and others . . . and lipid #trialists @DLBHATTMD , @cpcannon, & @VCUDPOSChair . . . and others, who are FOLLOWING @cardiomet_ce for expert-led #MedEd with 🆓CE/#CME! Tot ziens!
— cardio-met (@cardiomet_CE) August 26, 2023