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Cracking Down on Cholesterol

Heba El-Ahmad

Doctors everywhere are facing a common problem when trying to administer treatments:

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patients are neglecting to take their medicines. Why is this happening? It is one drug in particular
that seems to be so intolerable to warrant a complete disregard for health: cholesterol- lowering
Statins. These drugs may be cheap and effective, but as many as 25% of those who take Statins
experience muscle pain, hazy memory, or sleep problems (Kolata). Approximately 73.5 million
adults (31.7% of adults) in the United States have high concentrations of low- density lipoprotein
(LDL) cholesterol (commonly known as bad cholesterol) in the blood, and less than half of
these adults are getting treatment to lower their levels. This neglectful behavior nearly doubles
their risk of contracting heart disease, a risk that could easily be eliminated if an alternative to
these Statin drugs was found (High Cholesterol Facts). Today, the most common form of
treatment for high LDL cholesterol (LDL-C) is a group of drugs called Statins, but due to their
inability to provide a safe treatment for all those with high cholesterol, a superior class of drugs,
the PCSK9 inhibitor, is emerging with increased effectivity and decreased side effects.
Statins are currently the most common class of medicine used to treat high cholesterol.
By reducing blood cholesterol levels, Statins reduce chance of chest pain (angina), heart attack,
stroke, and other cardiovascular problems. Unfortunately, many side effects of Statin plague
those who need the drug for survival. These include the development of headaches, pins and
needles, abdominal pains, bloating, diarrhea, nausea, rashes, and severe muscle inflammation.
Studies have also shown that Statins may also raise cataract risk by 27%, and, when used in
combination with other drugs that carry high rhabdomyolysis (muscle damage) risk, cause liver
failure and skeletal muscle damage. Because of this, people with liver disease are not able to take
Statins at all, while those who suffer from many of these other side effects may not be able to
take the drug dosage necessary to lower their LDL-C to the necessary level. It is also
recommended that people taking Statins should not combine them with protease inhibitors

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(AIDS treatment), erythromycin, itraconazole, clarithromycin, diltiazem, verapamli, or fibrate

drugs (that also lower LDL levels). This puts a large population in a position where they may
need to lower blood cholesterol, but they are unable to do so for fear of encountering lethal side
effects. For those able to tolerate it, Statin is an effective therapy to lower LDL-C levels by
inhibiting HMG-CoA-reductase; however, even after intensive therapy there still remains a risk
of myocardial infarction 20-30% of the time, and many patients have also observed a
development of a statin intolerance within their bodies. It is clear that these Statin drugs are not
the ideal solution to a potentially deadly condition that plagues many Americans today (Crosta).
A possible future therapy is the proprotein convertase subtilisin kexin 9 (PCSK9)
inhibitor which has had great success in lowering lipid levels. The PCSK9 enzyme is mostly seen
in the liver and intestines and is an inhibitor of LDL receptors (LDLR), a pathway that LDL-C is
normally cleared out of the bloodstream through. LDL-C binds to LDLR on the surface of liver
cells, leaves the blood stream, and is then internalized into the liver cells while LDLR returns
back to the cell surface to repeat the process. When introduced, PCSK9 binds with the LDLR on
the surface of the cell and promotes the degradation of LDLR, preventing it from recycling back
to the surface of the liver cells. This decreases the amount of LDL-C being absorbed, increasing
LDL-C levels in the bloodstream. This new class of drug, PCSK9 inhibitors, stops the binding of
PCSK9 with the LDLR, preventing the degradation of the LDLR and allowing for more LDLR
available to remove LDL-C from the bloodstream. It was observed that a gain of function by
gene mutation of PCSK9 led to an elevation of LDL-C, while loss of function led to a decrease
in LDL-C, providing the rationale that the development of PCSK9 inhibitors would ultimately
lower LDL-C levels, eventually dramatically reducing cardiac risk. The three currently
prominent PCSK9 inhibitor drugs- Alirocumab, Evolocumab, and Bococizumab- have been

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shown to reduce LDL-C by over 50% in most patients (Gupta), and no adverse consequences
have been found that relate to the loss of PCSK9 (Peterson et al.).
Cardiology is the study and treatment of heart disorders that involves caring for anything
associated with the heart and the arteries, and one of the main topics of focus in the field of
cardiology is the study of cholesterol. High LDL cholesterol is a problem that can be observed in
every cardiologists office in almost every patient. A condition with such a large range of affected
persons should and needs to have a safe, reliable medicine for its treatment. Unfortunately,
Statins cannot provide the optimal treatment those affected need, but there is a solution. PCSK9
inhibitor drugs are the future of cardiology medicine, and hold great promise in effectively
treating the 73.5 million adults in the United States that suffer from high concentrations of lowdensity lipoprotein cholesterol in the blood (High Cholesterol Facts).

Sources:

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Crosta, Peter. "What are Statins?" Medical News Today (2015): n. pag. Print.
Gupta, Sanjiv. "LDL Cholesterol, Statins and PCSK 9 Inhibitors." Indian Heart Journal 67.5
(2015): 419-24. Print.
"High Cholesterol Facts." Center for Disease Control and Prevention. U.S. Department of
Health & Human Services, 17 Mar. 2015. Web. 5 Feb. 2016.
<http://www.cdc.gov/cholesterol/facts.htm>.
Peterson, Andrew S., Loren G. Fong, and Stephen G. Young. "PCSK9 Function and Physiology."
Journal of Lipid Research 49.6 (2008): 1152-56. Print.
"What is Cholesterol?" National Heart, Lung, and Blood Institute. National Institute of Health,
2010. Web. 5 Feb. 2016. <http://www.nhlbi.nih.gov/health/health-topics/topics/hbc>.