1b) @lipiddoc is a #lipidologist🩺🧬@nyulangone @NYUCVDPrevent. He is President of the Foundation of @nationallipid, Past-President of both @nationallipid AND @LipidBoard, and is Director of @BHLipidClinic. @cardiomet_CE is proud to welcome @lipiddoc as new faculty!
— cardio-met (@cardiomet_CE) September 25, 2023
3a) The symposium and this tweetorial were supported by an unrestricted educational grant from Novartis. Statement of accreditation & faculty disclosures at https://t.co/gvXca4G9Xm.
— cardio-met (@cardiomet_CE) September 25, 2023
👉Earn MORE 🆓CE/#CME from prior #tweetorials in this space archived at https://t.co/gMHi5FYTek.
4) Lp(a) (lipoprotein[a]) is a strong & independent risk factor for #CAD, #stroke, & #aorticstenosis. As Lp(a) levels are nearly 💯% genetically determined, strategies to control them are limited, but as a measurable biochemical marker of risk for #ASCVD, it is an important 🎯. pic.twitter.com/7gp0KnqFzt
— cardio-met (@cardiomet_CE) September 25, 2023
6a) Look at these illustrative distributions of Lp(a) (red) & LDL-C (blue) concentrations. Dashed vertical lines are shown at 50th and 90th percentile for each lipoprotein.
— cardio-met (@cardiomet_CE) September 25, 2023
🔓 https://t.co/srgm1RJUYI pic.twitter.com/qj36SjyVVd
6c) If a patient has elevated #LDL_C levels but indicators of #ASCVD risk are persistent despite effective #LLT such as #statins, one must consider the possibility of additional risk from elevated Lp(a), which is not ⬇️ by statins.
— cardio-met (@cardiomet_CE) September 25, 2023
7b) This is different from #statin #intolerance, about which you can learn and earn additional 🆓CE/#CME at https://t.co/mNBRJzoYGM and other programs at https://t.co/gMHi5FYTek.
— cardio-met (@cardiomet_CE) September 25, 2023
9) #Inclisiran is a fully chemically modified, #siRNA conjugated to the triantennary N-acetylgalactosamine (GalNAc). siRNAs are 1 type of #oligonucleotide therapeutic, targeting RNA directly (in this case #mRNA), destroying it before the protein is synthesized.
— cardio-met (@cardiomet_CE) September 25, 2023
10b) #Inclisiran has been demonstrated to have extremely potent & durable effects: a single SC injection can lower a patient’s #LDL-cholesterol level for 6 months. The #ORION-11 trial showed that #inclisiran also reduces Lp(a) levels.https://t.co/evuFz1Grt2
— cardio-met (@cardiomet_CE) September 25, 2023
11b) The safety data were reassuring: majority of events in each trial were reported to be mild or moderate, with the most common AEs occurring with similar frequency in the #inclisiran & placebo groups. Liver & kidney function effects also similar. pic.twitter.com/nVSt0JPbAg
— cardio-met (@cardiomet_CE) September 25, 2023
13) But what about safety of #inclisiran in comparison with those #PCSK9 antibodies, #alirocumab & #evolocumab? @vijay_nambi & Ali Agha MD addressed this. #siRNA and #MAbs have similar safety, https://t.co/4ATREmUmKX: pic.twitter.com/C5SoonAH6E
— cardio-met (@cardiomet_CE) September 25, 2023
15) So success (= safety + efficacy) + clinical need (elevated Lp(a) levels ➡️ residual risk after statins) brings more drug development programs to the fore. Are the other #ASO or #siRNA therapies that may safely lower Lp(a)?https://t.co/jBlldGmSii pic.twitter.com/YyjaD4GQJV
— cardio-met (@cardiomet_CE) September 25, 2023
17) #Pelacarsen & #olpasiran are farthest along.
— cardio-met (@cardiomet_CE) September 25, 2023
Pelacarsen is a Lp(a) antisense oligonucleotide #ASO also known as IONIS-APO(a)-LRx, AKCEA-APO(a)-LRx , & TQJ230. It inhibits production of apo(a) in the liver ➡️direct approach for reducing Lp(a).
🔓https://t.co/yDcwqA9wVZ pic.twitter.com/QHu7Wo3lbO
19) Here's where we are in #pelacarsen development, per https://t.co/bu0H0dbzip. The "big 🐶" is #HORIZON, published by @calvinyeang et al in @JACCJournals at 🔓 https://t.co/dRMUdfhyG3. pic.twitter.com/C1h0vhySag
— cardio-met (@cardiomet_CE) September 25, 2023
20b) Most AEs were mild or moderate; #SAEs 10% vs 2%, respectively. There was no dose-dependency pattern for AEs. 5% of pts on #pelacarsen & 4% of pts on placebo d/c'd participation for AEs.
— cardio-met (@cardiomet_CE) September 25, 2023
21) Now, #Olpasiran (formerly #AMG890). As the name implies, it is like #inclisiran a #siRNA. It ⬇️#lipoprotein(a) synthesis in the liver. See @DrM_ODonoghue et al in
— cardio-met (@cardiomet_CE) September 25, 2023
🔓https://t.co/xmnRPD6VpM pic.twitter.com/73MTb7d7Yd
23) Safety 🛟 from that trial #OCEAN(a)? Overall incidence of #AEs & #SAEs was similar among pts treated with #olpasiran and those on placebo. The incidence of AEs leading to the discontinuation of olpasiran or placebo was similar across the trial groups (2% in each group). pic.twitter.com/7fRo0nWBtZ
— cardio-met (@cardiomet_CE) September 25, 2023
24b) Phase 1 data 🔓https://t.co/mlewCnk8Fe: in 32 participants with elevated Lp(a) levels and no known cardiovascular disease: #SLN360 was well tolerated, and a dose-dependent lowering of plasma Lp(a) concentrations was observed. pic.twitter.com/D8ggmXWXRV
— cardio-met (@cardiomet_CE) September 25, 2023
25b) (cont)
— cardio-met (@cardiomet_CE) September 25, 2023
🦺 The #inclisiran safety profile is similar to that of the #PCSK9i mAb’s
🛟 Low Lp(a) seems to have no negative effects
🦺Assessment of safety and AE profiles of #siRNA-mediated lowering of Lp(a) to date suggest good tolerability
26b) The answer is c; they are about the same. Remember this from tweet 13? pic.twitter.com/lXvS2JPK33
— cardio-met (@cardiomet_CE) September 25, 2023
27b) It's c. #LDL-C levels are available on standard "lipid panels," but measurement of Lp(a) requires specialized testing. See excellent review by #FlorianKronenberg at 🔓 https://t.co/sCECc2tCgn. pic.twitter.com/6Pz0rvDzOz
— cardio-met (@cardiomet_CE) September 25, 2023
28) Great job! You just earned 0.5hr 🆓CE/#CME credit. Claim your certificate NOW at https://t.co/o1n3xJHXwj. Then click your 🖱️just ONCE MORE and FOLLOW US for more expert-led, always 🆓#MedEd! Thanks to @lipiddoc for being today's faculty!
— cardio-met (@cardiomet_CE) September 25, 2023