PCSK9 Inhibitor, Evolocumab, Efficient in Treating Peripheral Artery Disease

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 given in 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.

Treatment

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.

Evolocumab

Evolocumab 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.

"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 these patients."

References:

1. 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

Source-Medindia