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

Dr Brad Stanfield

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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...
VESALIUS-CV Diabetes Subgroup Analysis — JAMA 2026

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

3. doi: 10.1056/NEJMoa054013
https://www.nejm.org/doi/full/10.1056...
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...
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.ja...
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...
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...
Evolocumab in Patients without a Previous Myocardial Infarction or Stroke (VESALIUS-CV) — NEJM 2025

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

9. https://www.peoplespharmacy.com/artic...
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/19081...
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...
Ez-PAVE Trial — NEJM 2026

12. https://www.tctmd.com/news/very-low-l...
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.ja...
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...
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...
Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia — JAMA 2025

16. https://www.utsouthwestern.edu/newsro...
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.ja...
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

The content contained in this video, and its accompanying description, is not intended to replace viewers’ relationships with their own medical practitioner. Always speak with your doctor regarding the content of this channel, and especially before using any products, services, or devices discussed on this channel.

20 Comments

@DrBradStanfield Creator 5 months ago (edited) Pinned

🩺 Get your personalized health plan: https://drstanfield.com/pages/roadmap

@Corkfish1 5 months ago

A 2024 study indicated that ezetimibe, a common cholesterol medication, may be associated with a sevenfold lower risk of developing Alzheimer's disease and related dementias

@drillbabydrill892 5 months ago

3:14 Yes a 20% relative risk reduction, but only a 1.5% absolute risk reduction. Might be useful to mention that.

@purpleblueunicorn 5 months ago

This is huge. My LDL was 120 on a perfect wfpb diet, barely no saturated fat except the little in nuts or oats. A 10mg crestor reduced my LDL to 50. Only reason my cardiologist accepted to give it to me was because I had high LPa. Didn't want to give me ezetimibe because of false fear of pancreatitis. There's no reason to have ASCVD anymore. And btw, no side effects, no inflammation, middle aged endurance athlete.

@petersawchukux700 5 months ago

I’m wondering how we are to look at Apo b when all these studies are focused on LDL? I thought Apo b was a more accurate indicator.

@ancesthntr 5 months ago (edited)

I am definitely a cardiac patient, as I had a heart attack roughly 20 months ago. After having done an awful lot of reading, I have had a number of very “enthusiastic discussions“ with my cardiologist about reducing my statins. He finally agreed to cut my rosuvastatin in half, provided that I would t lake Ezetimibe l. I have been doing so since, and I’m waiting to see the results in my next round of tests before my appointment next month. As a side benefit of Ezetimibe, it apparently also reduces the incidence of dementia. So you really get three benefits from it: reduced LDL, reduced risk of dementia, and you can cut back on statins that have potentially harmful side effects. That it is as cheap as dirt only puts some icing on that cake.

@zackbremer1 5 months ago

how did we as humans ever survive ...even on a vegan diet with a good exercise regimen achieving an LDL of below 55 is very difficult. So now ALL the studies say EVERYONE even younger(30s) healthy people with no ASCVD, no metabolic derangement's, etc need to be on life time drugs? Why dont the researchers look into the 75% of people(that you mentioned) that had heart attacks with normal cholesterol levels...seems like that might be slightly more useful then putting teenagers on drugs for their cholesterol.

@gregt5794 5 months ago (edited)

Every few years the guidelines for cholesterol levels are lowered.

Extremely low ldl cholesterol (<50 mg/dL) as per Harvard Health and the Mayo Clinic state that the risks of the following health issues are increased:

1. Hemorrhagic stroke
2. Depression
3. Anxiety
4. Cancer
5. Cognitive impairment
6. Neurodegenerative diseases
7. Immune System Disorders
8. Nutritional deficiencies and absorption issues
9. Anemia
10. Adrenal failure
11. Aortic dissection
12. Diabetes type II

We cannot allow cardiology to take preference over all other medical fields to our detriment.

Before medications for cholesterol lowering were available CVD was the leading cause of death.

From the late 1950s medication to lower cholesterol became available and from 1987 statins became available and since then new and stronger statins have been introduced and the dosages increased in order to comply with the new guidance every few years - and what is the leading cause of death today, STILL CVD.

Something does not add up and you don’t need to be a doctor or a researcher to see that.

@olyav5819 5 months ago

Thanks for the update!

@kapurar 5 months ago

Great information that is fantastically presented! Really appreciate your channel and the information you share. Cheers! 🇨🇦

@DuncanWalshover40workouts 5 months ago

Enjoyed the talk as usual

@tarlkudrick1174 5 months ago

Oh, this war isn't over, Doctor. Medicine, like every other field, really only advances one funeral at a time.

@edsinofsky 5 months ago

great story and presentation.

@mattlm64 5 months ago

I'd like to see a study for people with moderately elevated LDL but otherwise have healthy blood markers with high HDL, low triglycerides, normal blood pressure and healthy body fat. The results could be entirely different.
Also, these drugs might have effects outside of LDL that provide benefit such as improving HDL to triglyceride ratios.

@toddboothbee1361 5 months ago

Thanks for the great information and the few pleonasms.

@DAH-ss1nu 5 months ago

No mention of Berberine? It's a pcsk9 inhibitor too.

@squidsanonymous275 2 months ago

I've been going through different studies trying to understand cholesterol and I've just got to say thank you for compiling all this data. This video is such a good reference.

@ThoughtMachine1 5 months ago

IMPORTANT:

As of January 2026 Repatha was approved for primary prevention. 80% of insurance companies no longer even require pre-authorization, just a prescription. With the Amgen copay card, cost to patient is capped at $17 / month.

@znojnyj 3 months ago

Sick work doc

@StepDub 5 months ago

The people who exhibit immunity to various diseases should be studied far more thoroughly. Back in the beginning of the Covid outbreak it was observed that certain people appeared to just shrug it off.
When the vaccines arrived, this line of research seems to have fallen by the wayside.
Seems a shame because there was probably a lot more that could have been learned from this line of investigation, and not just about the covid virus.