- Results of clinical trial FOURIER,
show that addition of PCSK9 inhibitor evolocumab to statin therapy reduces cardiovascular risk.
- Evolocumab works by drastically
reducing LDL cholesterol, which is a risk factor for cardiovascular
- Evolocumab efficacy is especially
beneficial to people affected by peripheral artery diseases as they are
at high risk for heart-related diseases.
The FOURIER trial
(Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects
with Elevated Risk) was a large study that determined the clinical use of PCSK9 inhibitor evolocumab
addition to standard statin therapy
. The results of the study were
presented at the 2017 American Heart Association Scientific Sessions by Marc
Bonaca, MD, MPH, investigator at the TIMI Study Group and director of the
Aortic Disease Center at Brigham and Women's Hospital. The study is published
in the journal Circulation
Peripheral Artery Disease (PAD)
Peripheral Artery Disease
is a circulatory problem
where the blood circulation to the lower limbs is limited due to narrow arteries.
Patients with PAD are at heightened risk of major adverse cardiovascular events
including myocardial infarction, stroke, and cardiovascular death. PAD is also
majorly associated with major adverse limb events including acute limb ischemia
and major amputation. It is usually caused due to fatty deposits in the
arteries called atherosclerosis
Despite the best treatments using high-intensity statins, the risk of cardiovascular and limb events remains high. While
low-density lipoprotein (LDL) cholesterol, a modifiable risk factor for
cardiovascular disease, has been studied in association with atherosclerosis,
very few studies show its efficiency in treating PAD patients.
is a member of a new class of
cholesterol-lowering drugs known as PCSK9 inhibitors. This group of drugs have
emerged as an effective treatment in lowering LDL to an extent that is not
possible by statin therapy alone. Evolocumab
reduces LDL cholesterol levels by approximately 60%.
FOURIER Clinical Trial
FOURIER was a very large trial involving 27,564 patients with either
atherosclerosis, PAD, myocardial infarctions, stoke and other conditions in 49 countries, who were on statin
therapy. The aim of the trial was to determine if the addition of evolocumab to
standard statin therapy reduced the risk of adverse
cardiovascular events. This was a randomized trial where some received
evolocumab while others received the placebo. Patients were observed for
approximately 2.5 years for cardiovascular and limb events.
After analysis of the FOURIER data, it was found that evolocumab
reduced the risk of cardiovascular disease in patients with and without PAD. As
patients with PAD are at a higher risk of a heart attack and stroke, these
patients had a higher absolute risk reduction of 3.5% while patients without
PAD had a 1.6% reduced risk of a cardiovascular event. The risk of major
adverse limb events was reduced to half in patients who received evolocumab
compared to PAD patients who received the placebo. In PAD patients who had no
history of a heart attack or stroke, evolocumab reduced risk of a
cardiovascular or adverse limb event by 6 percent over 2.5 years. The usage of
evolocumab was not associated with any concerning safety issues.
‘Evolocumab, a PCSK9 inhibitor lowers LDL-cholesterol by 60% and when administered in addition to statin therapy reduces risk of cardiovascular and limb events.’
"Whenever trials like FOURIER demonstrate benefit of a therapy
in a broad population, we then want to understand the efficacy and safety in
subpopulations to help clinicians understand which patients are going to derive
the greatest absolute benefit. We've found that several sub-groups of patients
respond well to evolocumab, but it's especially encouraging to see these
results for patients with PAD since this is a population at heightened
cardiovascular risk and there are few therapies that modify limb risk,"
said Bonaca. "We see that adding evolocumab can make a big difference for
- Bonaca, M. et al. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). CirculationCIRCULATIONAHA.117.032235 (2017). doi:10.1161/circulationaha.117.032235