Summary
The Peter Atia Drive podcast episode 4 focuses on cholesterol regulation and the drugs used for it. The discussion covers various drugs, including statins, ezetimibe, fibrates, fish oil, niacin, and the most recent class of drugs called PCSK9 inhibitors. The speaker emphasizes the complexity of the cholesterol synthesis pathway and the humility of drug development.
The podcast discusses the challenges of studying atherosclerosis due to the success of statins. The speaker also discusses the failure of trials involving ezetimibe in reducing events related to aortic stenosis and chronic renal failure. The speaker believes that reducing LDL levels can lead to extra event reduction and praises the success of PCSK9 inhibitors.
The discussion revolves around the effectiveness of fibrates in reducing LDL particle count and increasing HDL particle count, which has a statistically significant tie-in to the clinical endpoint. The fibrates help eliminate HDL particles and increase reverse cholesterol transport, which facilitates the removal of cholesterol from the artery wall.
The podcast also discusses the use of niacin and PCSK9 inhibitors in lowering LDL cholesterol levels. The speaker mentions that niacin, while previously popular, has not shown significant benefits and can cause adverse reactions such as flushing and pruritus. The speaker also discusses the genetic model of PCSK9 inhibitors, which enhance the clearance of LDL particles and can lead to a reduction in coronary heart disease.
Finally, the podcast discusses the impact of cholesterol synthesis inhibition on organs, particularly the brain. The speaker argues that while statins are still an important tool for reducing cholesterol, they should be used thoughtfully and in conjunction with monitoring of serum desmosterol levels. The speaker emphasizes the importance of nuanced thinking and individualized treatment plans, rather than a one-size-fits-all approach to lipid-lowering therapy.
