PCSK9 inhibitors do not work.

CHOLESTEROL LOWERING DRUGS - CONTINUED ..

Since the purpose of Western Medicine is to make money, we have various classes of medications to reduce cholesterol levels in the blood, and these supposedly reduce incidence of heart attacks, as per the £vidence. The ''£vidence'' is produced by “$cientists” who are paid $$ by Pharmaceutical Corporations, or Professors from universities such as Oxford and Stanford who are also paid $$$ to publish in prestigious journals (whose funding mainly comes from Pharmaceutical Companies). 

There are various classes of such drugs:

1. STATINS - these are the most widely prescribed drugs in medical practice. Almost all my patients are on statins, even if they have not had a heart attack/stroke. Doctors recommend that every one who breathes oxygen should take a statin, as it is a life saving drug. There are around 36 trials on statins, and most of them show no benefits, increased death in the treatment groups, and dangerous side effects. Read my article on statin research here. 
2. BILE ACID BINDERS such as ezetemibe. As per this trial, this drug can reduce heart attacks by 1%. Amazing!
3. INCLISIRAN
4. PCSK9 inhibitors - this is a new class of drugs that inhibits the release of LDL into the bloodstream by inhibiting a protein called PCSK9 in the liver. They are a relatively new drug, but VERY EFFECTIVE at reducing your LDL levels to really low numbers. I will explore the evidence on this drug in this article.

What is PCSK9?

It is a very important protein that is part of the lipoprotein system (LDL, HDL etc).

It plays a role in regulating LDL levels during times of infection and stress. It also helps with brain neuron development, skin barrier formation, etc. [wikipaedia on functions here]. Please see my article on the function of lipoproteins here. Think of how your tonsils or your bone marrow produces white blood cells during an infection? PCSK9 produces LDL during an infection - as LDL is part of the innate immune system.

The medical establishment claims that cholesterol is bad for you (particularly the cholesterol present within the LDL protein, and Lp(a) protein), and that we must reduce it to as low a number as possible in order to prevent and treat heart disease. This way of thinking is dogmatic, and not necessarily based on logic or scientific evidence. There is plenty of contradicting evidence to the idea that LDL, or that the cholesterol within LDL is bad for you. I have explored this in another article, but bear in mind:

• most people with heart attacks do not have high LDL cholesterol levels, but often have low HDL levels. There is no useful drug to increase HDL levels, so doctors ignore this. Interestingly, if you eat a low-carb high healthy-fat diet, your HDL goes up A LOT. But doctors ask you to eat high-carb (grains) diet with low fats and recommend unhealthy fats (seed/vegetable oils and margarines). 
• low LDL-C levels increase risk of heart failure, cancer, dying from infection & all cause mortality.
• those with high LDL C live longer (particularly centenarians). Those with familial hypercholesterolaemia (a genetic issue where their total cholesterol goes up to 500) actually live longer IF they do not smoke or have diabetes. Here is a link to the evidence on those with FH, presented by Dr David Diamond. There is more evidence explored by Dr Uffe Ravnskov and he has written various books about it, too. Unfortunately the man is too old to continue more research - I e-mailed him!
• Lastly, there is a class of drugs called SGLT2i - which is being used by cardiologists extensively. It has been shown to reverse kidney disease, heart failure, prevent heart attacks, and even reduce dementia risk! If a drug reverses plaques and reduces heart attacks, you would expect that it will reduce your cholesterol levels. But, it does the opposite- increases your LDL cholesterol. Personally, I am quite impressed with the evidence on this drug - literally double the number of patients in placebo have heart attacks compared to drug treatment group! STUDY linked here. I have failed to see such results with statins.

PCSK9 drugs are a class of drugs that reduce your LDL-cholesterol levels to almost 0. For example, in the trail I explore below, LDL cholesterol dropped from 118 to 48 mg/dL.

• PCKS9 inhibitors reduce LDL levels to near 0. If LDL causes heart attacks, then PCSK9 drugs should completely eliminate heart attacks, and at least reduce your risk of death! 
• Please note that heart disease is one of the leading causes of death in the world. If LDL causes heart disease, then reducing LDL to almost 0 should eliminate heart disease, thereby save lives.
• What we find from the studies is that PCSK9 drugs have NO mortality benefits. As in - DEATH is not prevented. The absolute risk reduction of heart attacks is very low, almost insignificant (around 1%).
• This paper is a meta-analysis of all the trials on PCSK9 inhibitors. There are about 20 trials below:

^ The above summary is directly copied from this paper comparing all the trials.

• PLEASE look at the cardiovascular events in the treatment group vs placebo group. There is barely any difference in heart attacks between the treatment group and placebo group. Moreover, there is no mortality benefit (DEATH has not been prevented)
• All of these trials are conducted by Pharma, so they have their own biases. They have probably manipulated data to find some sort of benefit. Despite of their best effort, the results are unimpressive.
• In the FOURIER trial, for example - there is INCREASED CARDIOVASCULAR mortality in the treatment group. This was found only when data was re-analysed by independent scientists [link to study here]. 
• I have not analysed each and every trial, but an alarming thing I noticed was that most of the trials are really short - around 12 weeks (3 months). This is not long enough to study outcomes!

ANALYSIS OF THE LONGEST TRIAL ON THIS DRUG (17 months - which is not that long!)

I have analysed below the LONGEST trial done on PCSK9 inhibitors: ODYSSEY LONG TERM is a 17 month trial, the longest we have got. I have directly copy pasted this info from the New England Journal of Medicine. 

LDL-lowering capacity of the drug: EXCELLENT! It drops LDL from 118 to 48 mg/dL (This is nearly zero)

Given that this drug has destroyed all of the cholesterol in your LDL proteins, and that we believe LDL causes heart disease, the results should be astonishing - there should be a MASSIVE reduction in heart attacks!

I have copy pasted the following paragraphs from the paper:

RESULTS OF THE STUDY:

In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02).

STUDY CONCLUSION - The of major adverse cardiovascular events (a composite end point of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was 48% lower among patients who received alirocumab than among those who received placebo during the 80 weeks of follow-up (nominal P=0.02). When all adjudicated cardiovascular events were included (i.e., with the addition of congestive heart failure requiring hospitalization and ischemia-driven coronary revascularization), the difference between groups was not significant.

TRANSALATION TO ENGLISH rather than scientific jargon:

• HIGHLIGHTED IN BLUE: The difference in heart problems between the 2 groups is 1.6% (3.3% in the placebo group and 1.7% in the treatment group). This is not that great, and could be attributed to chance. They then, in the conclusion claim that the events were reduced by 48%.This is called statistical deception - a very commonly used methodology to exaggerate benefits of drugs. 1.7 as a number is 48% less than 3.3. But the actual reduction in events is only 1.6%
• HIGHLIGHTED IN GREEN: They mention that they have EXCLUDED 2 events from their outcome analysis - this includes heart failure and heart attacks that needed stenting!
  I repeat - they have excluded 2 very important outcomes from the results. Once you count these events, there is ZERO benefit to the drug. The drug should reduce ALL types of heart attacks. It does not matter if it increases some types and decreases some type.
• CORRECT CONCLUSION: There is ZERO cardiovascular benefit to giving this drug to a patient for 17 months. It even increases heart attacks that require admission and stenting (this is bad)
• Another issue I noted in the trial data is that in the placebo group, the HDL levels went down slightly. This might be due to placebo pill containing sugar, for instance. But any drop in HDL levels can increase heart disease risk. Therefore, automatically the placebo group is at higher risk of heart disease, and the data between placebo and drug becomes UNEQUAL.
• ALSO NOTE: Statin trials are also similar with respect to lack of any benefit, lack of long-term trials, and increased death in the treatment groups.

CONCLUSION By Dr. Hannah Mathew (myself, and no I am not paid by anybody):

• If you, a pharmaceutical company have $$$, then you can produce $cience papers using $cientific jargon and $cientific names of $cientists from prestigious Universities. Then, you can publish them in prestigious $cientific journals that you have paid $$$ to publish, and you can literally make up random numbers of apparent benefits by skewing and manipulating the dodgy data that you have produced. You can also write conclusions that are directly contradictory to your experiment results. (Like in this study, the drug shows no benefits whatsoever - even shows harm.) These conclusions will be read by doctors and guideline committees who practice €vidence ba$ed M€dicine! Look below at who is funding these $cientists, and note how the manuscript has been updated and edited using scientists who work for the Pharma company! 
• Note that these drugs are expensive, costing around $5000 per year. The stress of these costs will definitely increase your risk of heart attack, all for a net benefit of ZERO.

• New England Journal of Medicine, is trash - take it from ex- editor in chief Dr Marcia Angell, a professor of medicine at Harvard Medical School.