I Treat Cholesterol Differently Now: Statins, PCSK9s, Ezetimibe & Gene Editing

About This Episode

There is a drug in clinical trials right now that could permanently fix your cholesterol with a single infusion. Once. That's where we're headed. But there's also a $4 generic that's saved millions of lives — and a twice-a-year injection most patients have never heard of. I'm a Stanford-trained physician. My ApoB was 128. My grandfather died of a stroke. My grandmother died of cardiac arrest. My father is recovering from a heart transplant. In this video, I break down every lipid-lowering option available — without hedging, without liability speak — so you can have an intelligent conversation with your doctor. *WHAT YOU'LL LEARN:* - Why there's no floor for ApoB — the cholesterol-years concept that changes when you start treatment - The genetics checkpoint: Lp(a), FH, and ancestry factors that change your drug selection entirely - Statins: muscle pain reality, the nocebo effect (SAMSON trial), SLCO1B1 gene, CAC paradox, diabetes signal - Ezetimibe: the most underused $15/month drug in lipid medicine (IMPROVE-IT data) - Bempedoic acid: why it structurally cannot cause muscle toxicity, and what CLEAR Outcomes proved - PCSK9 inhibitors: FOURIER + ODYSSEY data, insurance battle, patient assistance programs - Inclisiran: twice a year, doctor administers — why adherence changes everything - Lp(a) pipeline: pelacarsen, olpasiran, muvalaplin — what's coming for the 1 in 4 - Obicetrapib: oral pill hitting BOTH LDL and Lp(a) - Gene therapy: CRISPR + base editing — one injection, once in your life - Lifestyle: honest ceiling assessment, no guilt - A tiered protocol framework using ApoB as the treatment target - What to actually say to your doctor — 6 specific questions *Chapters:* 0:00 The cholesterol treatment playbook 05:11 Genetics Checkpoint 07:51 Statins 16:16 Ezetimibe 18:45 Bempedoic Acid 25:46 PCSK9 Inhibitors 37:20 Inclisiran 39:46 Lp(a) 44:00 Emerging Therapies + Gene Therapy 52:32 Lifestyle 56:11 Protocol Framework 59:04 What to Say to Your Doctor *LINKS:* Part 1 — The Disease (Atherosclerosis): https://youtu.be/fX33g1zFZSo Part 2 — The Testing (Why Your Lipid Panel Isn't Enough): https://youtu.be/AtOTY0x3U3I Part 4 — The Genetics: (COMING SOON) Newsletter — The Longevity Letter: https://www.hillarylinmd.com/subscribe Follow me: Instagram: https://instagram.com/hillarylinmd Twitter/X: https://twitter.com/hillarylinmd CareCore (For Clinicians): https://carecore.io DISCLAIMER: This video is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any medication or treatment. Drug dosing, insurance coverage, and clinical guidelines referenced in this video may have changed since filming. I am a physician but I am not your physician. KEY STUDIES REFERENCED: - CTT Meta-analysis: 170,000+ patients, 22% event reduction per 1 mmol/L LDL (Lancet 2012) - IMPROVE-IT: ezetimibe outcomes, 18,000 patients (NEJM 2015) - FOURIER: evolocumab, 27,500 patients, LDL median 30 mg/dL (NEJM 2017) - FOURIER-OLE: 8.6-year follow-up, no safety signal at LDL ‹ 20 (Circulation 2023) - ODYSSEY OUTCOMES: alirocumab, 18,924 post-MI patients (NEJM 2018) - SAMSON trial: 90% of statin symptoms also occurred on placebo (NEJM 2020) - CLEAR Outcomes: bempedoic acid, 14,000 statin-intolerant patients (NEJM 2023) - ORION-10/11: inclisiran, sustained 50-52% LDL reduction (NEJM 2020) - VICTORION-2P: inclisiran outcomes trial, ongoing - OCEAN(a) Phase 2: olpasiran, › 95% Lp(a) reduction (NEJM 2023) - Lp(a)HORIZON: pelacarsen outcomes trial, 8,000+ patients, ongoing - VERVE-101 heart-1: base editing PCSK9 (Lancet ~2024) - NTLA-2001 Phase 1: CRISPR PCSK9 editing (2024) - Ference et al.: Mendelian randomization, lifetime LDL (EHJ 2017) #cholesterol #ApoB #statins #PCSK9 #inclisiran #genetherapy #lipids #longevity #heartdisease #preventivemedicine #atherosclerosis #cardiovascular #LDL #lipidplaybook