Evolocumab, when added to statin therapy, reduced LDL cholesterol by 59 percent in patients with cardiovascular disease, the first completed outcomes trial of a PCSK9 inhibitor showed. The results also found that the drug reduced risk of adverse cardiovascular outcomes with greater benefit the longer the duration of therapy.

Insurance companies will be struggling, however, with whether that benefit justifies the drug’s list price of almost $15,000 per year.

PCSK9 inhibitors are a new class of cholesterol lowering drugs. They have emerged as an effective treatment for drastically lowering LDL cholesterol beyond what is possible with statin therapy alone. Previous research demonstrated that evolocumab, a member of this new class of drugs, effectively reduces LDL cholesterol by approximately 60 percent.

Lead researcher Marc S. Sabatine, MD, MPH, chairman of the TIMI Study Group at Brigham and Women’s Hospital, said:

“The use of evolocumab, in combination with statin therapy, effectively lowered LDL cholesterol down to a median of 30 mg/dL and resulted in clinically meaningful benefits that increased the longer patients received the therapy."

Evolocumab And Statin Therapy

The FOURIER trial (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) was designed to determine whether evolocumab, when added to statin therapy, would reduce adverse cardiovascular events.

In the randomized, double-blind, placebo-controlled multinational clinical trial, 27,564 patients aged 40-85 were studied. All trial participants had stable atherosclerotic vascular disease, defined as a medical history of heart attack, strokev or symptomatic peripheral artery disease.

On a background of high or moderate intensity statin therapy patients had a LDL cholesterol level of at least 70 mg/dl. Patients received either evolocumab (140mg every two weeks or 420mg every month) or placebo.

Similar to data from previous lipid lowering trials, researchers report that evolocumab reduced LDL cholesterol by 59 percent, in this case from a median of 92 mg/dL to a median of 30 mg/dL. The LDL cholesterol lowering effect remained constant over the duration of the trial.

15 Percent Risk Reduction

Researchers report that patients treated with evolocumab (brand name Repatha) had a 15 percent reduction in the risk of major cardiovascular events, defined as the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization (occurring in 9.8 percent of patients treated with evolocumab vs. 11.3 percent of patients treated with placebo).

Additionally, evolocumab reduced the more serious key secondary endpoint, which was a composite of heart attack, stroke or cardiovascular death, by 20 percent (occurring in 7.9 percent of patients treated with evolocumab vs. 9.9 percent in the placebo group). This reduction in risk improved over time, increasing from 16 percent in the first year to 25 percent after the first year.

“Importantly, the reduction in events was consistent across all key subgroups, including age, sex, type of disease and statin intensity,” said Sabatine.

The data also show similar clinical benefit with evolocumab when analyzed according to baseline LDL levels, even in patients in the lowest quartile of baseline LDL cholesterol, in whom evolocumab reduced LDL cholesterol from 73 to 22 mg/dL.

Repatha is a fully human monoclonal antibody that works by blocking proprotein convertase subtilisin-kexin 9 (PCSK), a protein that reduces the liver’s ability to remove LDL cholesterol from the blood, and was approved for use in the United States in 2016 as an addition to statin therapy and lifestyle changes aimed at lowering LDL cholesterol in some adults with cardiovascular disease.

Marc S. Sabatine, M.D., M.P.H., Robert P. Giugliano, M.D., Anthony C. Keech, M.D., Narimon Honarpour, M.D., Ph.D., Stephen D. Wiviott, M.D., Sabina A. Murphy, M.P.H., Julia F. Kuder, M.A., Huei Wang, Ph.D., Thomas Liu, Ph.D., Scott M. Wasserman, M.D., Peter S. Sever, Ph.D., F.R.C.P., and Terje R. Pedersen, M.D., for the FOURIER Steering Committee and Investigators Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease NEJM March 17, 2017 DOI: 10.1056/NEJMoa1615664

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