Exploring Lipid-Lowering Medications and the Role of Fibrates

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)

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Simon Hill, MSc, BSc (Hons)

• Creator of theproof.com
• Host of The Proof with Simon Hill
• Author of The Proof is in the Plants

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