by Duane Graveline, MD, MPH
In 2015, the U.S. Food and Drug Administration (FDA) approved the first two drugs of a new class of cholesterol reducing agents known as PCSK9 inhibitors.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring protein in humans that binds to the receptors for low-density lipoprotein (LDL) cholesterol in the liver. By inhibiting PCSK9, more LDL receptors are made available to attach to the LDL particles, thus reducing the amount of serum LDL cholesterol circulating in the body.
Although PCSK9 inhibitors are not statins, they are designed to be used in conjunction with statins for those patients that do not experience the expected drop in LDL cholesterol from statins alone.
They are also intended as an alternative method for reducing LDL cholesterol for the statin intolerant. Many of those that start taking statins have to stop taking them due to muscle pain and weakness alone.
The first two PCSK9 inhibitors to be approved — Sanofi/Regeneron’s alirocumab (Praluent) and Amgen’s evolocumab (Repatha) — may have competition soon with Pfizer’s bococizumab currently in late stage clinical trials.
Approval for the marketing of alirocumab and evolocumab was granted only on the basis of LDL cholesterol reduction (which PCSK9 inhibitors do extremely well). At the time of approval, there was no evidence presented of any long term survivability or cardiovascular benefit for either of these biopharmaceutical drugs.
Clinical trials to determine whether these drugs prevent either heart attacks or early death from cardiovascular disease are ongoing at this time.
So approval for these PCSK9 drugs was granted with no proven health benefit, an unknown long-term side effect profile, and at an annual cost more than 50 times higher than a generic statin.1
It is shocking to me that a drug could obtain approval based only upon treating a number, particularly when so many studies have shown that higher cholesterol equates to lower all-cause mortality.
Surely there should have been trials showing actual benefit to those taking these drugs before releasing them for widespread use. How many of these early adopters realize that rather than taking a proven safe and effective drug that can extend their lives, they are part of an experiment with an uncertain outcome.
The results of the ongoing trials will be reviewed with much interest. As PCSK9 inhibitors work in an entirely different way than statins, there is no mevalonate blockade. So CoQ10, dolichols and selenoproteins, unlike with statins, will not be affected. This would suggest an improved side effect profile is possible.
However, there will be no anti-inflammatory benefit that is seen with statins and the same problems associated with artificially lowered cholesterol can be expected.
One of the negative effects of lowering cholesterol is cognitive issues. As we know, the healthy human brain is just 5% of body weight but contains over 25% of the body’s cholesterol.
Remember also that cholesterol is an essential part of cell membranes keeping them fluid and maintaining their structural integrity.
Cholesterol is also critical for the production by the body of steroid hormones like those responsible for regulating blood sugar levels, maintaining normal blood pressure levels and production of the sex hormones.
To create vitamin D from sunlight requires cholesterol and the body’s ability to make bile acids to digest fats also relies on cholesterol.
I fear that all the drug companies are going to do with this, besides make money, is create incredible numbers of cognitive disorders of all kinds.
Neurocognitive problems, such as mental confusion or trouble paying attention, have already been noted to be present in some of the study participants receiving PCSK9 inhibitors.2
The PCSK9 monoclonal antibodies cut LDL cholesterol levels by an average of roughly 60% compared with placebo or standard therapy.3
Whatever our median serum cholesterol level has been during the time period 2004-2012 of our statin era, nearly 10,000 cases of transient global amnesia or severe memory loss have been reported to Medwatch during that time (4,809 cases of transient global amnesia and 4,235 cases of severe memory deficit).4
Imagine the impact on this marker when the median level of serum cholesterol approaches 50, the expected target level of LDL cholesterol when this new class of drug is used along with statins like atorvastatin and simvastatin plus Zetia.
In the original clinical trials for alirocumab, neurocognitive disorders were seen in those taking the drug compared to placebo.5 These neurocognitive disorders included amnesia, memory impairment and confusional state — just what is seen with the use of statins.
So if you have two drugs, both independently capable of producing the same side effects, imagine what happens when you combine them. I cannot think of any act more guaranteed to cause neurocognitive chaos.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
4. FAERS Statin Review https://www.spacedoc.com/articles/faers-statin-review