#407 ‒ Preventing cardiovascular and Alzheimer's disease: lowering LDL early, APOE4, and promising new therapies | Michael Davidson, M.D.

**Peter Attia** (0:11)
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My guest this week is Michael Davidson. Michael is a cardiologist, lipidologist, and the founding CEO of New Amsterdam Pharma. He is a recognized leader in lipidology, having coordinated more than a thousand clinical trials, published over 350 peer-reviewed papers, and authored three books on lipid disorders and cardiovascular prevention. His work spans statins, novel lipid lowering therapies, omega-3 fatty acids, and cardiovascular drug development. He also founded several biotech companies and clinical research organizations, including the Chicago Center for Clinical Research, Omthera Pharmaceuticals, and Corvidia Therapeutics. Michael also previously served as the president of the National Lipid Association.
Michael's career has spanned the intersection of lipid science, prevention, and drug development.
With Obesetrapib, he is now at the center of one of the most important open questions in cardiology, whether CTEP inhibition can finally deliver meaningful reductions in LDL, ApoB, LpA, and ultimately cardiovascular risk. In this episode, we discuss how Michael's family history shaped his career in lipidology and prevention. LDL is a causal driver of atherosclerosis, and why it should be treated more like blood pressure or smoking, the history of CTEP inhibitors, why earlier drugs failed, and what makes Obesetrapib different. Obesetrapib's effect on LDL cholesterol, ApoB, LDL particle number, LpA, diabetes risk, and cardiovascular outcomes. How Obesetrapib may fit alongside statins, azetamide, PCSK9 inhibitors, and other lipid-lowering therapies. The complicated biology of HDL, brain cholesterol metabolism, ApoE4, and the potential role for Obesetrapib in Alzheimer's prevention, and omega-3 fatty acids, DHA delivery to the brain, AI in clinical trials, and the future of drug development for cardiovascular and neurodegenerative diseases. So without further delay, please enjoy my conversation with Michael Davidson.
Michael, thank you so much for coming out. It is hard to believe that this is our first meeting in person, given how many years we've worked together electronically and in other ways.

**Michael Davidson** (3:23)
Right. Yes. Great to be here, Peter.

**Peter Attia** (3:25)
For folks who might not be familiar with your work, although we've certainly referenced it a lot on the podcast, your work speaks for itself, so you certainly don't need us referencing it. Maybe tell folks a little bit about yourself, starting with what you do clinically.

**Michael Davidson** (3:38)
I'm a cardiologist, lipidologist. I run the lipid clinic at University of Chicago. I'm a professor, so I see patients actually four full days a month, and that's a pretty loaded prevention-focused practice.

**Peter Attia** (3:51)
What's the path to that? Because lipidology is not necessarily a subspecialty within cardiology, although of course people who listen to this podcast are very familiar with it, and Tom Dayspring has been on a number of times. But what was your path towards that from your training? Were you always interested in prevention?

**Michael Davidson** (4:06)
It's a passion because my father died at age 47 of a heart attack. I was 16
I had abnormal lipids, ran into my family, so I got very interested in lipids in medical school. So I did the original niacin trials that went back into the 80s, late 70s actually, and then after training residency, I started doing research in my fellowship on omega-3 fatty acids for the lipid effects. I was the first one to use fish oil capsules to treat lipid disorders. And then from there, I got involved all the statin trials. It's been my passion is to be involved in clinical trials. And I'm still a cardiologist, did the usual stuff that cardiologists do, and then focused primarily on prevention. So I opened a prevention center out of my fellowship, along with a research company that did all the clinical trials. And that's been my path ever since. And then the biotech startups started happening about 15 years ago.

**Peter Attia** (5:02)
We have some overlap in some of those companies, one of which we'll talk about. But maybe even before we get into some of the really exciting things going on in pharma, maybe we can just speak a little broadly about prevention, because there really isn't, at least as I see it, a uniform consensus around how aggressively one should be trying to prevent ASCVD. Sometimes I feel like people look at me as though I have multiple heads. When I talk about taking steps towards prevention in 30-year-olds, for example, because by any calculable metric, their 10-year risk is very low and would not necessarily justify the steps we might take.