Outlive: The Science and Art of Longevity

by Peter Attia

While there are seven statins on the market, I tend to start with rosuvastatin (Crestor) and only pivot from that if there is some negative effect from the drug (e.g., a symptom or biomarker). My goal is aggressive: as rationalized by Peter Libby, I want to knock someone’s apoB concentration down to 20 or 30 mg/dL, about where it would be for a child. For people who can’t tolerate statins, I like to use a newer drug, called bempedoic acid (Nexletol), which manipulates a different pathway to accomplish much the same end: inhibiting cholesterol synthesis as a way to force the liver to increase LDLR and therefore LDL clearance. But where statins inhibit cholesterol synthesis throughout the body, and most notably in the muscles, bempedoic acid does so only in the liver. Therefore, it does not cause the side effects associated with statins, especially muscle soreness. The main issue with this drug is cost. Another drug called ezetimibe (Zetia) blocks absorption of cholesterol in the GI tract.[*10] That in turn depletes the amount of cholesterol in the liver, leading once again to increased LDLR expression and greater clearance of apoB particles, which is what we want. Ezetimibe pairs very well with statins because statins, which block cholesterol synthesis, tend to cause the body to reflexively increase cholesterol reabsorption in the gut—exactly the thing that ezetimibe so effectively prevents.