2) The #LBCTs excerpted here were selected by 3⃣international experts on #LLT: Alan Brown MD MHA FACC FNLA @alanbrownmd, Peter P Toth MD PhD FCCP FAHA FESC FACC, & returning faculty Pam R. Taub MD FACC FASPC @PamTaubMD while onsite together at #AHA25. pic.twitter.com/4vtjzc4GUx
— cardio-met (@cardiomet_CE) November 24, 2025
3b) See statement of #accreditation and faculty disclosures at https://t.co/gvXca4G9Xm.@MedTweetorials @CardioNerds @nationallipid #cardiotwitter #Hyperlipidemia #Lipids #ASCVD #AHA25 @ASPCardio @society_eas
— cardio-met (@cardiomet_CE) November 24, 2025
4b) What was a 🔑finding of the #VESALIUS_CV trial of #evolocumab?
— cardio-met (@cardiomet_CE) November 24, 2025
a. ⬇️ risk of 1st major #CV event in high-risk pts without prior MI/stroke
b. No signif ⬇️in CV events vs placebo
c. Benefit limited only to pts with prior MI/stroke
d. ⬆️risk of #SAEs w/long-term evolocumab
5a) So let's move on to those #AHA2025 late breakers! Perhaps the most anticipated #LLT data in #NewOrleans was from #VESALIUS_CV. This trial explored potential benefit of the #PCSK9i #evolucumab vs placebo in patients at high risk for #ASCVD but WITHOUT a prior #MI or #stroke. pic.twitter.com/jxDS8ByidH
— cardio-met (@cardiomet_CE) November 24, 2025
5c) The trial was designed to eval > 12K such pts, esp those with ASCVD & high-risk #diabetes, w/ #hyperlipidemia despite optimized #statin +/- #ezetimibe, randomized to biweekly #evolocumab vs placebo for dual primary #EPs of 3⃣- & 4⃣-point #MACE over a median of 240 wks pic.twitter.com/ceJxzxAqEs
— cardio-met (@cardiomet_CE) November 24, 2025
6) So before we get to those clinical endpoints, take a look at the impact of #evolucumab on #LDL_C over time–a 55% reduction vs placebo achieved as early as 48 weeks and then maintained: pic.twitter.com/DMOSTNUxFV
— cardio-met (@cardiomet_CE) November 24, 2025
7b) Results were likewise consistent in important subgroups, including in those w/ #diabetes + no qualifying #atherosclerosis.
— cardio-met (@cardiomet_CE) November 24, 2025
And, there was no evidence of a between-group difference in the incidence of #AEs ➡️ d/c of evolocumab or placebo, or in the incidence of #SAEs. pic.twitter.com/nOTQVf0n6U
8) Moving on now to another #LBCT, but sticking w/the theme of #PCSK9i, we saw at #AHA25 the 1st Ph 3 results of a once-daily ORAL PCSK9i 💊, #enclitide decanoate, on top of background #LLT. These came from the #CORALreef trial presented by Ann Marie Navar of @UTSWMedCenter. pic.twitter.com/7TJUvr7Y55
— cardio-met (@cardiomet_CE) November 24, 2025
10) The #CORALreef population was 39% ♀️, 50% diabetic, mean age 62, & 58% had already had a major #ASCVD event. ~88% finished the study & dropout due to an #AE was similar #enclitide & placebo. Mean #LDL_C at entry was 96mg/dL & 97% were on #statins, 26% on #ezetimibe. pic.twitter.com/fydCgeiFfh
— cardio-met (@cardiomet_CE) November 24, 2025
11b) At 24wk they also saw significant ⬇️in non-#HDL, #apoB, & Lp(a) with ~53%, ~50%, & ~28% ⬇️respectively . . . and all with excellent tolerability, solid adherence, & good safety compared to placebo: pic.twitter.com/WxNk2IWBCY
— cardio-met (@cardiomet_CE) November 24, 2025
12a) Reaction? Our expert authors were impressed! The convenience of a daily 💊w/ nearly 60% placebo-adjusted #LDL_C ⬇️, matching the potency of injectables: major potential in particular for #statin-intolerant pts. One concern: outside an RCT, would adherence be as high?
— cardio-met (@cardiomet_CE) November 24, 2025
13a) And now for something completely different: A #triagonist! Yes, from 🇨🇳 we saw Ph 2 results w/#DR10624, a 1st-in-class #FGF21 receptor/#Glucagon receptor/#GLP-1 receptor triple agonist in pts w/severe #hypertriglyceridemia #SHTG. pic.twitter.com/DHaOOtlvR6
— cardio-met (@cardiomet_CE) November 24, 2025
13c) 79 pts (avg age 46), 89% ♂️, 100% Asian, were enrolled. Baseline TG all ⬆️⬆️ at 500-2000 mg/dL.
— cardio-met (@cardiomet_CE) November 24, 2025
~30% took TG-lowering meds throughout the 12wk study.
Pts randomized 3:1 #DR10624:pbo & outcomes were lipid panels + #MRI_PDFF scans for liver fat.
2 groups were well matched. pic.twitter.com/WDJuARhcOm
14b) 78.5% of #DR10624 pts had >50% ⬇️in #TGs over 12wk, vs 5% on Pbo.
— cardio-met (@cardiomet_CE) November 24, 2025
DR10624-treated pts also had signif improvements in total #cholesterol, high-density #lipoprotein cholesterol, non-HDL cholesterol, TG-rich lipoprotein cholesterol, other #atherogenic lipids, & metabolism. pic.twitter.com/NeDoq1S6tS
14d) Patients treated with #DR10624 had a 63.5% ⬇️in liver fat, vs 8.4% with Pbo. The effect was evident across all dose groups, and the liver fat scans showed the dramatic difference in effect: pic.twitter.com/QOi7CuzwuE
— cardio-met (@cardiomet_CE) November 24, 2025
15a) The authors concluded that #DR1064 was safe, well tolerated, and effective over a 12wk period in pts w/#SHTG, and that longer follow-up in a Ph 3 study is warranted. A trial in pts with #MASH may also be reasonable. pic.twitter.com/9JcrRPWSF2
— cardio-met (@cardiomet_CE) November 24, 2025
15c) Peter Toth: #FGF21R is an exciting & novel 🎯; it regulates energy homeostasis & is an #insulin sensitizer. Add it to #glucagon & #GLP1 agonism ➡️great potential for favorable metabolic action. He is esp impressed w/liver fat that built up over yrs was cleared in 12wks.
— cardio-met (@cardiomet_CE) November 24, 2025
17a) These pts are at high risk of acute #pancreatitis. They were randomized to #olezarsen 50mg (#CORE), 80mg (#CORE2), or placebo, & were tx'd for 1yr. Primary EP: % change fasting #TG, baseline ➡️6mos. pic.twitter.com/p4eJMf0twT
— cardio-met (@cardiomet_CE) November 24, 2025
18a) So here are the primary EP: % change in fasting #TG baseline to 6mos, and the #pancreatitis secondary EP. Both are strikingly positive for #olezarsen (vs placebo). TG reduction was rapid & was sustained over 12 mos: pic.twitter.com/8BIUSv1Xh7
— cardio-met (@cardiomet_CE) November 24, 2025
18c) Other #lipid endpoints and safety parameters were all reassuring and are shown here: pic.twitter.com/Oja3omDzmp
— cardio-met (@cardiomet_CE) November 24, 2025
19) @alanbrownmd points out that this is the first time we have seen a signif ⬇️in acute #pancreatitis (85% reduction vs pbo) in pts w/#SHTG, and notes that added to #SOC, 86% of pts tx'd w/#olezarsen reached #TG levels < 500 and up to 54% achieved normal TG of <150mg/dl. pic.twitter.com/vW638MA18n
— cardio-met (@cardiomet_CE) November 24, 2025
21a) So here researchers looked at 15 pts from 🇦🇺🇳🇿. Focused on safety, they also monitored for % ⬇️ in #LDL_C, #TG, #apoB, #apoC3, non-#HDL_C, & remnant cholesterol after a single dose of #CTX310. The #LBCT presentation had only early biomarker data. pic.twitter.com/GB7OmdlzCN
— cardio-met (@cardiomet_CE) November 24, 2025
21c) Here are the time course plots showing stable ⬇️in #ANGPLT3 and ⬇️ in multiple lipid levels. pic.twitter.com/mbcSK0R7CM
— cardio-met (@cardiomet_CE) November 24, 2025
22) All of that with solid safety as evaluated by #DILI ⤵️, and per the simulpub in @NEJM , no dose-limiting toxic effects or #SAEs related to #CTX310 were observed.
— cardio-met (@cardiomet_CE) November 24, 2025
See https://t.co/gQ6Im0g8Wj. pic.twitter.com/ral6RbvqKh
24) And on that rather philosophical note, we'll wrap up this "lipid-palooza" from #AHA25. You can grab 0.75hr 🆓CE/#CME right now by clicking ur 🖱️on https://t.co/IUJmDpPx7B. Yes, it's that easy! Please follow us for more expert-led #MedEd! pic.twitter.com/dFNeUQPsx4
— cardio-met (@cardiomet_CE) November 24, 2025