2) Not all pts w/ #hyperlipidemia & associated #CV risk can tolerate #statins, & others are statin-refractory. Much research on non-statin alternatives. @DrMarthaGulati, #cardiologist @CedarsSinai is a leader in this space & is President of @ASPCardio.#FOAMed #CardioTwitter
— cardio-met (@cardiomet_CE) April 8, 2024
4a) So we'll start with some updates on the seminal #CLEAR_Outcomes trial. Don't recall that? Refresh your memory & earn even more 🆓 #MedEd credit 🇺🇸🇨🇦🇪🇺🇬🇧from experts @CMichaelGibson @cpcannon @PamTaubMD @ErinMichos @ProfKausikRay at https://t.co/gMHi5FYTek. pic.twitter.com/9ATiynykq7
— cardio-met (@cardiomet_CE) April 8, 2024
5) We have had 3⃣ 🆕secondary analyses presented at #ACC24 from #CLEAR_Outcomes, continuing to flesh out the importance of these data. First was presented by Leslie Cho @ClevelandClinic & addressed characteristics & outcomes for #statin-intolerant ♀️receiving #bempedoic_acid.
— cardio-met (@cardiomet_CE) April 8, 2024
6b) This is important unmet need because ♀️ are less likely to have #hypercholesterolemia dx'd or tx's AND are more likely to report #statin #intolerance https://t.co/xie61As1KB 👇, but #CV outcomes data in women are scarce. pic.twitter.com/gGqieUYlsh
— cardio-met (@cardiomet_CE) April 8, 2024
6d) CLEAR-Outcomes:
— cardio-met (@cardiomet_CE) April 8, 2024
🫀 total n= 13,970 participants at high CV risk with statin-intolerance
♀️ 6740
♂️ 7230
randomized to 180 mg of bempedoic acid daily or placebo
Looking here at primary EP of #MACE-4 (as above) using a Cox proportional hazard model pic.twitter.com/dCZdRKRgxc
6f) The authors conclude that in #CLEAR_Outcomes:
— cardio-met (@cardiomet_CE) April 8, 2024
1⃣ no heterogeneity in the effect of bempedoic acid on #CV risk by sex
2⃣ overall incidences of #SAE, #AEs, AEs leading to DC, & changes in laboratory parameters did not differ meaningfully between ♀️ and ♂️.
6h)
— cardio-met (@cardiomet_CE) April 8, 2024
♀️ Let other trials learn from #CLEAR_Outcomes: enroll adequate numbers of women into trials!#ACC24
Read more about this work TODAY at 🔓https://t.co/8n1XwV3YMd
8a) As we have seen, in #CLEAR_Outcomes #bempedoic acid ➡️significant ⬇️#LDL_C & ⬇️ #CV risk in statin-intolerant ppl with, or at high risk for, #CVD by 13%. #Hispanic/#Latinx ppl have been underrepresented in clinical trials investigating lipid & #ASCVD management.
— cardio-met (@cardiomet_CE) April 8, 2024
8c) And here is the primary EP by ethnicity shown as Kaplan-Meier graph and in table: pic.twitter.com/9TMqpwCG4M
— cardio-met (@cardiomet_CE) April 8, 2024
8e) .@DrMarthaGulaticomments: 17% of this trial was Hispanic/Latinx: more than most trials to date
— cardio-met (@cardiomet_CE) April 8, 2024
📌As we will see later, despite no difference in outcomes by race, we have differences in access to #bempedoicacid by race, especially for Hispanic & Black persons
9) Finally, at #ACC24 we heard from Harold E Bayes, MD, of of Louisville Metabolic & Atherosclerosis Research Center address the differential impact of #bempedoic acid among #obese vs non-obese participants in #CLEAR_Outcomes–another pre-specified secondary analysis.
— cardio-met (@cardiomet_CE) April 8, 2024
10b) Given that ⬇️ing #LDL-C with proven agents ⬇️ #CVD risk, pts at high CVD risk w/ #obesity & #hypercholesterolemia may benefit from a dual approach of interventions that promote both ⬇️in LDL-C & weight ⬇️. See
— cardio-met (@cardiomet_CE) April 8, 2024
🔓 https://t.co/3GCiFUI0bO
🔓 https://t.co/9YRQDIMmxL
10d) Compared to placebo at 6 mos, #bempedoic acid ⬇️reduced #LDL-C by 22.5% (95%CI -23.7, -21.2) & #hsCRP by 23.2% (-26.1, -20.3) in pts with BMI ≥ 30 kg/m2. #MACE_4followed suit.
— cardio-met (@cardiomet_CE) April 8, 2024
⚖️Pts in both groups tended to lose weight over the course of the study. pic.twitter.com/XRgWr06s2k
10f) The authors concluded that compared to placebo among patients with #obesity, #bempedoic_acid reduced #MACE-4 by 23%, lowered #LDL-C by 22.5% and #hsCRP by 23.2%, and was generally well tolerated in #CLEAR_Outcomes.
— cardio-met (@cardiomet_CE) April 8, 2024
11a) There was exciting news on the #lipidmanagement front outside of #bempedoic_acid as well. In a #LBCT at #ACC24, @BrianBergmark of @TIMIStudyGroup presented primary results of the #BRIDGE– #TIMI_73a trial. pic.twitter.com/PTuIPIEn76
— cardio-met (@cardiomet_CE) April 8, 2024
11c) Here's the situation: Lipoprotein lipase #LPL hydrolyses #TGs & facilitates clearance of #TRLs. #Apolipoprotein_C_III resides on TRLs & inhibits LPL ➡️ ⬆️ TG levels.
— cardio-met (@cardiomet_CE) April 8, 2024
🔎We know that loss of function mutations in #APOC3 ➡️ ⬇️#TG levels & ⬇️ #CV risk. pic.twitter.com/wGsiriUzZN
11e) In Ph 2 #RDBPC dose-ranging study in 114 pts w/ high #TG (baseline median fasting TG 262mg/dl), TG were significantly ⬇️ by 23% (10mg q 4wks), 56% (15mg q 2wks, and by 60% w/ both 10mg qw & 50mg q 4wks.) TG ⬆️ by 6% in placebo group. See 🔓 https://t.co/lqxHqwcNed. pic.twitter.com/w4QipvqCcp
— cardio-met (@cardiomet_CE) April 8, 2024
11g) ⬆️ plasma #TG assoc'd w/multiple pro-atherogenic & metabolic co-morbidities, including #T2D, low #HDL_C, #hypertension, #obesity, & ⬆️inflammation.
— cardio-met (@cardiomet_CE) April 8, 2024
👉Modest ⬆️TG ➡️ risk factor for #ASCVD; higher levels worse + ⬆️ risk of acute #pancreatitis.
See 🔓 https://t.co/k9P3Wk6wDq.
12b) Here are enrollment/disposition details and baseline characteristics of the study population: pic.twitter.com/UdBn4V0e3q
— cardio-met (@cardiomet_CE) April 8, 2024
13b) 🗝️ subgroups showed consistent efficacy, and multiple other lipid levels improved significantly (except #LDL and #TC, but that's consistent with the #MOA), including markers indicative of atherogenesis pic.twitter.com/gPOKciERku
— cardio-met (@cardiomet_CE) April 8, 2024
15) #ACC24 presentation by @BrianBergmark acknowledged these limitations: pic.twitter.com/B0f2X01wU4
— cardio-met (@cardiomet_CE) April 8, 2024
16b) #Olezarsen led to meaningful reductions in #apolipoprotein_B and non-#HDL #cholesterol, which are markers of atherogenic risk. And a robust development program is in progress. pic.twitter.com/4mLxq5dZXZ
— cardio-met (@cardiomet_CE) April 8, 2024
18) .@DrMarthaGulati comments on BRIDGE TIMI-73a: The results of this Phase 2b trial, which will of course require validation in a larger Phase 3 study, show ⬇️TG levels of ~50%, a clinically meaningful effect not seen with currently available therapy. This bears watching!
— cardio-met (@cardiomet_CE) April 8, 2024
20) The authors, from @UTSWInternalMed, note that early uptake of #PCSK9i #mAbs was limited by payer rejections & out-of-pocket (OOP) costs. During the 1st year of availability:
— cardio-met (@cardiomet_CE) April 8, 2024
💰52.8% of pts Rx'd PCSK9i never received approval
💰34.7% of pts approved PCSK9i abandoned the Rx
22a) N=116,176 prescribed #bempedoic acid
— cardio-met (@cardiomet_CE) April 8, 2024
👉median age 67, 56.6% female
👉Of those prescribed BA:
💰31.1% never received insurance approval
💰12.1% were approved but never filled the Rx pic.twitter.com/Yn15YOmFdx
22c) Commercial insurance, #cardiologist as prescriber (vs primary care), and high provider prescription volume were associated with greater likelihood of #bempedoic acid Rx approval. pic.twitter.com/6eyGiJVSvS
— cardio-met (@cardiomet_CE) April 8, 2024
24) #Cardiology providers and provider Rx volume are associated with improved approval rates, suggesting the potential that provider familiarity through education and support during the prior approval process may improve overall prescription success.
— cardio-met (@cardiomet_CE) April 8, 2024
25b) The (in)correct response is B. In fact, there was no heterogeneity in the effect of #bempedoic_acid on #CV risk by sex. The other statements are true.
— cardio-met (@cardiomet_CE) April 8, 2024
25d) The (in)correct answer is C. In fact, patients with obesity in CLEAR-Outcomes treated with bempedoic acid #BA experienced significant reductions in both MACE-3 and MACE-4. #ACC24
— cardio-met (@cardiomet_CE) April 8, 2024
25f) The only correct answer is A. Indeed the opposite statement of the other options is true! Pts on #olezarsen had similar rates of thrombocytopenia & bleeding, has similar glycemic control, and had similar renal function during study compared with placebo.
— cardio-met (@cardiomet_CE) April 8, 2024
26) And it's just as if you were here in the #ATL for #ACC24–thanks to @DrMarthaGulati for bringing these #LLT highlights to us. You can now claim your 🆓 full 1⃣ hr of CE/#CME credit by clicking on https://t.co/0tMlAUJchg. Then FOLLOW US for more expert-led #MedEd! pic.twitter.com/tV4XZ5pzUQ
— cardio-met (@cardiomet_CE) April 8, 2024