Today I will be writing about an overview of some of the current medication available for lowering LDL cholesterol, as well as some medication that is no longer used.

I have already explained all the different types of cholesterol, or lipoproteins [here](https://tinyurl.com/bdz67ekp), and what fat actually is [here](https://tinyurl.com/32ahwcps). I will just say here that lowering cholesterol actually means lowering LDL cholesterol. There is currently no available medication that can increase your HDL (which should be a good thing).

**1. Statins**. Statins are some of the most prescribed drugs in modern medicine. Every healthy patient that is evaulated as having a "high" risk of heart disease should be prescribed a statin according to most guidelines - we call this primary prevention. Every heart attack survivor should be prescribed a maximum tolerated statin dose according to most guidelines - we call this secondary prevention. As of 2023, Lipitor is the 2nd most profitable drug in history. There is still enormous money to be made pushing statin prescriptions, despite the expired patent.

Since we have known for at least 50 years that dietary cholesterol does not significantly alter cholesterol levels in the blood, we needed to find a drug that would stop the body from creating its own cholesterol. Statins work by inhibiting the rate-limiting enzyme in cholesterol synthesis called HMG-CoA reductase. 

Statins do indeed work as advertised - they do a brilliant job of lowering LDL cholesterol. Unfortunately, like all other drugs, statins have their side effects. It is known that they cause muscle aches, are potentially toxic for the liver, and now we know they are linked to dementia and possibly other neurological diseases, and why wouldn't they be? Remember that cholesterol is a vitally important molecule - over 40% of the cell membrane is composed of cholesterol, the myelin sheath surrounding our nerves is made of cholesterol; vitamin D, and ALL steroid hormones are made from cholesterol.

But, as a patinent, the most important thing you can ask your doctor is: "But, doc, how much longer will I live if I take this drug?", which should, of course, be followed by: "What are the side-effects?".

The answer to the first question are in - you gain ~3 days of life per 5 years of treatment for primary prevention, and ~4 days of life per 5 years of treatment for secondary prevention of heart disease. You can look at the study [here ](https://bmjopen.bmj.com/content/5/9/e007118.long). So, if you take Lipitor for 30 years straight, you will, on average, live ~18-24 days longer. If statins were free candy with no side-effects, I would have no objections, but, alas, this is not the case. 

Should you take a statin? Nobody can answer that for you. However, you have the right and the obligation to be well informed. Ask your doctor what he thinks, and if he is dismissive, then find another doctor. Personally, I will never take a statin, even if I survive a heart attack/stroke.

Statins are the best drugs of all lipid-lowering agents because they at least show *some* benefit in reducing heart disease risk. This probably says a lot about the other drug classes we will be discussing next.

**2. Ezetimibe.** Remember how dietary cholesterol does not significantly alter blood cholesterol levels? Well imagine if you could reduce this small effect even further! Ezetimibe works by decreasing cholesterol absorbtion in the intestines. Does ezetimibe help lower LDL? Yes, yes it does. Does it affect overall mortality? [No, it does not](https://drnevillewilson.com/2008/02/04/the-enhance-trial-its-failure-concerns/). Ask your doctor how much longer will you live if you take ezetimibe - the answer is actually zero days. 

**3.PCSK9 inhibitors.** So, you are taking a statin and ezetimibe, and your cholesterol is still too high according to the ever lowering upper limit of acceptable cholesterol levels? No problem, we will give you an extremely expensive monoclonal antibody that will affect your LDL receptors. These drugs are a special class of useless. Not only do they cost a lot of money, they have a negative to no effect whatsoever on overall mortality. How much longer will you live if you take Repatha? Probably 0 days or less, but ask your doctor and they probably won't know.

To truly understand this, it might be a good idea to read "A Statin Nation" by coleague M. Kendrick. The efficacy of Repatha (A PCSK9 inhibitor class drug) was 'proved' in the FOURIER trial, which used something called 'composite end-points', meaning that the researchers packaged different, related clinical outcomes... with coronary revascularization, which isn't a clinical outcome. Yes, the FOURIER trial showed an improvement in the COMPOSITE end point of: cardiovascular death, cardiac infarction, stroke, unstable angina hospitalisation AND coronary revascularization; but the total number of OVERALL deaths and the total number of CARDIOVASCULAR-related deaths was higher in the Repatha group compared to placebo.

And this is it, we have currently three main drug classes that will reduce your LDL cholesterol levels, but I think we should mention another, forgotten, drug class as well.

**4. Trapibs.** Trapibs were a class of drugs that were in development in the mid to late 2000s, but were since scraped, abandoned and forgotten. We were not taught about them in med school. Abandoned drugs are just an unimportant footnote in medical school, anyway; which is a shame because a lot can be learned through studying failure. 
Anyway, trapibs affect the interaction of HDL and LDL particles through an enzyme called CETP. They ultimately increase HDL, which is good, and also lower LDL, which is also good. Here we have drugs that should work amazingly well on paper - they decrease LDL similar to statins, and they also increase HDL. Yet, their effect on overall and cardiovacular mortality is close to zero.

None of the above described LDL-lowering agents have a significant, if any, effect on overall mortality, yet we still continue prescribing them to patients. Sure, there were studies that found an association between high LDL levels and cardiovascular mortality; but there's a far stronger association with either diabetes, smoking, obesity and hypertension. You should always verify information for yourself, especially when it comes to health, but it is my opinion that lipoproteins are, at best, a mere marker of potential heart disease risk, and a complete red herring at worst. It's like the correlation between yellow fingers and lung cancer. Should we cut off yellow fingers? No, of course not. It just so happens that smokers usually get yellow fingers from excessive smoking. Should we reduce LDL cholesterol by substituting animal fats with industrial made seed oils? I leave that for you to decide.

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