Lowering cholesterol with medicine | Dr Thomas Dayspring and Dr Dan Soffer

In this episode, I’m joined by Dr Tom Dayspring and Dr Dan Soffer for a comprehensive look at lipid-lowering therapy. We unpack the science behind statins, ezetimibe, PCSK9 inhibitors, fibrates, and newer agents like bempedoic acid, asking what really works, who should take them, and how early treatment might prevent disease. From guideline thresholds to real-world decision making, historical trials to future therapies, this conversation offers clarity on one of the most important areas in cardiovascular prevention. In this episode, we cover: What lipid-lowering therapy actually is Statins, ezetimibe, fibrates, and PCSK9 inhibitors How these drugs work and who benefits most Absolute vs relative risk reduction explained Guidelines vs clinical practice Lipoprotein(a) and new therapies on the horizon A detailed yet practical discussion to help you cut through the noise and make sense of lipid-lowering therapies. Intro: What Are Cholesterol-Lowering Drugs and How Do They Work? (00:00:00) How Do Cholesterol-Lowering Medications Lower Heart Risk? (00:05:00) Who Should Start Statins or Other Cholesterol Drugs? (00:09:29) Landmark Cholesterol Trials That Changed Heart Disease Treatment (00:22:54) Do Fibrates Still Matter for High Triglycerides? (00:36:27) Ezetimibe & PCSK9 Inhibitors: Do They Add Benefits Beyond Statins? (00:42:30) CLEAR Outcomes Trial: What It Means for Statin-Intolerant Patients (00:52:02) Bempedoic Acid vs Statins: Effectiveness, Side Effects & Cost (00:53:45) What Do Statin Trials Really Show? Heart Attacks, Death & Risk Reduction (01:00:35) When to Use Low vs High-Intensity Statins (and Add Ezetimibe) (01:10:52) Hydrophilic vs Lipophilic Statins: What’s the Difference? (01:14:17) Do Statins Affect the Brain or Your Body’s Cholesterol? (01:19:03) PCSK9 Therapies Explained: Antibodies, siRNA, Oral Drugs & Gene Editing (01:24:28) What’s the Best Combination Therapy After Statins? (01:30:33) LDL Guidelines Explained: Thresholds vs Goals (01:32:49) The Most Up-to-Date Cholesterol Guidelines (2025) (01:40:25) This episode is brought to you by: 38TERA Consider 38TERA's DMN prebiotic supplement a daily multivitamin for your gut. Formulated by yours truly and gastroenterologist Dr Will Bulsiewicz. Use code THEPROOF for a discount at checkout. Fireflies Stay focused and let Fireflies handle the notes. From transcriptions and summaries to real-time voice commands, Fireflies turns your meetings into actionable insights, seamlessly integrating with Zoom, Google Meet, Slack, and more. Sign up for a yearly plan and get two months FREE at fireflies.ai/theproof. Bragg Bragg Organic Apple Cider Vinegar is raw, unfiltered, and naturally fermented with 100% organic apples, always with the live “Mother” in every bottle. Get 20% off your first order at bragg.com with promo code SIMON. IM8 With 92 nutrients, including Vitamin B12, Iodine, Selenium and Vitamin D, in highly absorbable forms, IM8 Daily Essentials is the perfect all-in-one daily multi-vitamin to ensure you meet your daily micronutrient needs. IM8 is offering an exclusive 10% off your first order with a free welcome kit when you enter the promo code SIMON at checkout on im8health.com WHOOP Whoop, the most advanced fitness and health wearable available. Your personalised fitness and health coach to recover faster, sleep better, and train smarter. Claim your first month free on join.whoop.com/simon. Simon Hill, MSc, BSc (Hons) Creator of theproof.com Host of The Proof with Simon Hill Author of The Proof is in the Plants Subscribe & Connect: YouTube Apple Podcasts Spotify Instagram: @simonhill Twitter: @theproof Facebook: The Proof with Simon Hill