The Cholesterol War Is Over (Here's Who Won)

Brad Stanfield

Apr 16, 2026

Episode description

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Timestamps:
00:00 The Dallas Heart Study and PCSK9
02:58 The Fourier Trial
03:34 The VESALIUS-CV Trial
08:21 The Case for Lower LDL Targets
08:26 The Ez-PAVE Study
10:13 The PESA Study
11:53 The Underutilization of Ezetimibe
13:22 Conclusion and Future Directions

Here are the links to the research papers referenced in the video:
1. doi: 10.1001/jama.2026.3277
https://jamanetwork.com/journals/jama/fullarticle/2847162
VESALIUS-CV Diabetes Subgroup Analysis — JAMA 2026

2. doi: 10.1172/JCI84086
https://pmc.ncbi.nlm.nih.gov/articles/PMC4607136/
JCI Conversation with Helen Hobbs — 2015

3. doi: 10.1056/NEJMoa054013
https://www.nejm.org/doi/full/10.1056/NEJMoa054013
Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease — NEJM 2006

4. doi: 10.3389/fcvm.2021.764038
https://pmc.ncbi.nlm.nih.gov/articles/PMC8589637/
Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications — Frontiers in Cardiovascular Medicine 2021

5. doi: 10.1016/j.jacc.2012.08.986
https://www.jacc.org/doi/10.1016/j.jacc.2012.08.986
Effects of AMG 145 on Low-Density Lipoprotein Cholesterol Levels — JACC 2012

6. doi: 10.1056/NEJMoa1615664
https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (FOURIER) — NEJM 2017

7. doi: 10.1056/NEJMoa2514428
https://www.nejm.org/doi/full/10.1056/NEJMoa2514428
Evolocumab in Patients without a Previous Myocardial Infarction or Stroke (VESALIUS-CV) — NEJM 2025

8. https://www.acc.org/About-ACC/Press-Releases/2026/03/28/15/33/Evolocumab-Cuts-Cardiac-Risk-in-Patients-Without-Known-Atherosclerosis-and-With-Diabetes
Evolocumab Cuts Cardiac Risk in Patients Without Known Atherosclerosis and With Diabetes — ACC Press Release, March 2026

9. https://www.peoplespharmacy.com/articles/woman-has-heart-attack-despite-very-low-cholesterol
Woman Has Heart Attack Despite Very Low Cholesterol — People's Pharmacy

10. doi: 10.1016/j.ahj.2008.08.010
https://pubmed.ncbi.nlm.nih.gov/19081406/
Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines — American Heart Journal 2009

11. doi: 10.1056/NEJMoa2600283
https://www.nejm.org/doi/full/10.1056/NEJMoa2600283
Ez-PAVE Trial — NEJM 2026

12. https://www.tctmd.com/news/very-low-ldl-levels-best-secondary-prevention-ez-pave
Very Low LDL Levels Best in Secondary Prevention: Ez-PAVE — TCTMD (Cannon + Aspry quotes)

13. doi: 10.1016/j.jacc.2017.10.024
https://www.jacc.org/doi/10.1016/j.jacc.2017.10.024
Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors (PESA) — JACC 2017

14. doi: 10.1177/11772719241257410
https://pmc.ncbi.nlm.nih.gov/articles/PMC11143858/
Are We Using Ezetimibe As Much As We Should? — Therapeutic Advances in Cardiovascular Disease 2024

15. doi: 10.1001/jama.2025.20620
https://jamanetwork.com/journals/jama/article-abstract/2841258
Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia — JAMA 2025

16. https://www.utsouthwestern.edu/newsroom/articles/year-2026/march-cholesterol-guideline-shifts-focus-earlier-prevention.html
Updated cholesterol guideline shifts focus to earlier prevention — UT Southwestern Newsroom, March 2026 (Rohatgi quote)

17. doi: 10.1016/j.jacc.2012.09.017
https://www.jacc.org/doi/10.1016/j.jacc.2012.09.017
Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease — JACC 2012

Thumbnail by James Kelly
Video edited by Troy Young
Script by John Milliken

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Mindsip insights from this episode:

Reevaluate normal cholesterol levels to ensure heart health

Almost 75% of patients hospitalized for a heart attack had LDL cholesterol levels that were considered within the recommended, 'safe' targets.

#cholesterol

#heart

Treat high cholesterol early to prevent heart disease

The latest research challenges the medical paradigm of waiting for atherosclerosis to appear, suggesting that treating high cholesterol intensively and early saves lives.

#cholesterol

#heart

Monitor LDL cholesterol levels to prevent plaque buildup

Observational data suggests that atherosclerotic plaque buildup only begins to occur when LDL cholesterol levels are above a threshold of approximately 50 to 60 mg/dL.

#LDL

#plaque

Leverage PCSK9 mutation to achieve low LDL and reduce heart disease risk

A rare genetic mutation that disables the PCSK9 gene can result in an extremely low LDL of 14 and an 88% reduction in heart disease risk.

#cholesterol

#genetics

Lower LDL to enhance longevity and reduce mortality risk

Aggressively lowering LDL to a median of 44 mg/dL in diabetic patients showed a preliminary signal for a 24% lower risk of dying from any cause.

#LDL

#longevity

Prescribe Ezetimibe to improve cholesterol management in cardiovascular patients

The cheap, generic, and effective cholesterol-lowering drug Ezetimibe is prescribed to only 6% of cardiovascular disease patients who could benefit from it.

#cholesterol

Aim for LDL below 55 mg/dL to reduce heart-related events

A clinical trial directly comparing LDL targets found that aiming for below 55 mg/dL instead of 70 mg/dL led to a 33% reduction in major heart-related events.