CCMS Medicine Winter 2017 - 22

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Indications
Current FDA approved indications:
1. Adjunct to diet and maximally tolerated
statin therapy for the treatment of adults with
heterozygous familial hypercholesterolemia.
2. Treatment of atherosclerotic cardiovascular
disease in those who require additional lowering
of LDL cholesterol despite being on the
maximum dose of statins.
3. Evolocumab (Rapatha) was also approved
as an adjunct to other lipid-lowering therapies
in patients with homozygous familial
hypercholesterolemia.

Major Studies
The Odyssey Combo 2 trial
Randomly assigned patients at high cardiovascular
risk and elevated LDL cholesterol, despite maximal
doses of statins, were treated with either Alirocumab
or Ezetimibe (both also receiving statins). At week
24 the Alirocumab group had a 50.6% reduction in
LDL cholesterol compared with a 20.7% reduction
for the Ezetimibe group.
GAUSS-2 trial
Patients at high cardiovascular risk who were statin intolerant were
randomly assigned to either Evolocumab or Ezetimibe groups after
12 weeks of LDL cholesterol reduction. The Evolocumab group
ranged between 53% and 56% compared with 37% to 39% for the
Ezetimibe group.
PCSK9 inhibitors have also shown a 50% to 60% reduction in
LDL cholesterol in patients with familial hypercholesterolemia.

Side Effects
The FDA issued a warning, published in March of 2014, about
the possible cognitive adverse effects of these drugs, but a review
published in 2015 concluded that these agents when used in patients
with high LDL cholesterol seem to be safe and effective. However,
significant side effects can occur and are somewhat similar in both
drugs.
The following potential side effects should be watched for:
1. Allergic reactions including local injection site reactions.
2. Runny nose, sore throat, cold or flu-like symptoms and
back pain.
3. Neurocognitive side effects such as mental confusion and
memory impairment can occur in less than one percent of
patients.
22 C H E S T E R C O U N T Y M e d i c i n e | W I N T E R 2 0 1 7

Who should get these drugs? The data is compelling,
but I would recommend following the FDA indications
closely. Exhaust the cheaper treatments before jumping to a
$15,000-a-year option but do not withhold use if the indications
are met. Hopefully, further studies [table 2] currently in the
pipeline which have more outcome data will increase the
indication spectrum. Moreover, as competition increases the cost
should also come down.
This article was a
collaboration between
Mian A. Jan, an
interventional cardiologist
practicing in Chester
County, and Zarshawn
Jan, a second-year
medical student at Drexel
University College of
Medicine.
http://chestercms.org/index.html
Table of Contents for the Digital Edition of CCMS Medicine Winter 2017
