In this episode of The Proof, I’m joined once again by two of the world’s leading lipid experts, Dr Tom Dayspring and Dr Dan Soffer. Together we take a deep dive into the world of lipid-lowering therapy: what these medicines are, how they work, and what decades of clinical trials reveal about their impact on cardiovascular health.
From statins and ezetimibe to PCSK9 inhibitors, fibrates, and beyond, we explore the mechanisms, safety profiles, and effectiveness of different therapies. We also cover the nuances of guidelines, primordial prevention, and whether people should consider treatment earlier in life. Along the way, Tom offers a fascinating historical tour through landmark trials, while Dan brings a clinician’s perspective on evidence-based practice and patient care.
What 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
- New therapies and future directions
- Lipoprotein(a): risk and emerging treatments
- And much more
This episode will help you better understand the medicines used to reduce cardiovascular risk and how they fit into the bigger picture of prevention and long-term health.
- 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)
Subscribe and stay connected:
Subscribe to The Proof on YouTube, Apple Podcasts or Spotify to ensure you never miss an episode. And don’t forget to follow me on Instagram and X for more insights and updates.
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.
References:
More about Dr Dan Soffer
Dr Soffer is a full-time clinician and educator Associate Professor of Clinical Medicine in the Associated Faculty of the Perelman School of Medicine at the University of Pennsylvania in the Department of Internal Medicine and Division of Translational Medicine and Human Genetics. He is the Director of Education for Preventive Cardiology and Clinical Lipidology at the University of Pennsylvania and co-Director of the Preventive Cardiology Fellowship program at Pennsylvania Hospital and co-director of the SOM Foundations of Culinary Medicine course.
He is a clinical lipid specialist whose focus is Preventive Cardiovascular Medicine. He is a Diplomate of the American Board of Internal Medicine and American Board of Clinical Lipidology, and Fellow of the National Lipid Association (NLA) and American College of Physicians (ACP) and he is a Member of the Academy of Master Clinicians at Penn Medicine.
Dr Soffer’s educational focus is on the impact of atherosclerosis on individuals, the community, and society, and the role of lipids and lipoproteins in this process, along with a special interest in inherited disorders of lipids and lipoproteins. His approach to education is to translate complex science into legible clear language and images that do not require advanced education to understand.
He is involved in multiple education activities at the University of Pennsylvania, the National Lipid Association (NLA), the Philadelphia Lipid and Atherosclerosis Club (PLAC)/Philadelphia Cardiovascular Institute, and commercial continuing medical education as well.
He is involved with multiple NLA activities including leadership, administration, education, meeting planning, and editing. He was President of the National Lipid Association (2023/2024) and President (2018/2019) of the Northeast Chapter of the NLA (NELA). He was co-editor of the NLA journal LipidSpin (2015-2020) and is an Associate Editor of the Journal of Clinical Lipidology as well as co-Director and lecturer for the Foundations of Lipidology course for the NLA. He is also the co-director of the Philadelphia Lipid and Atherosclerosis Club (PLAC). In addition to clinical medicine, teaching, writing, and editing, he also participates as an investigator in ongoing clinical research with lipid-modifying pharmacotherapies and population health initiatives.
He earned BA and MD from the University of Pennsylvania and Internal Medicine residency was completed at the Hospital of the University of Pennsylvania, and has practiced his entire career (since 1997) at Penn.
Dan has been married to Gwen since 1990 and they have three grown children together, Maddie, Ben, and Joe, and one Cavapoo named Petunia.
More about Dr Thomas Dayspring
Thomas Dayspring, who resides in the Richmond, VA area is a Fellow of both the American College of Physicians and the National Lipid Association and is certified in internal medicine, and clinical lipidology. After practicing in New Jersey for 37 years, in 2012 he moved to Virginia and served as an educational director for a nonprofit cardiovascular foundation and later as a Chief Academic Advisor for two major CV laboratories until mid-2019. Currently he is a virtual cardiovascular educational research assistant & clinical lipidologist at a prestigious national practice. Career-wise he has given over 4000 domestic (all 50 states) and international lectures, including over 600 CME programs on atherothrombosis, lipids/lipoproteins (and their treatment), vascular biology, biomarker testing, and women’s cardiovascular issues. He has authored several manuscripts and lipid textbook chapters and performed several podcasts. Until 2019 he was an Associate Editor of the Journal of Clinical Lipidology. He was the recipient of the 2011 National Lipid Association’s Presidents Award for services to clinical lipidology. He has over 25K followers on his educational Twitter feed (@Drlipid). He is a Social Media Ambassador for the European Atherosclerosis Society.
