The PCSK9 inhibitor dramatically reduces high cholesterol and cuts the risk of heart attack and stroke.
A landmark study revealed that the cholesterol-lowering drug evolocumab (Repatha) also reduces the risk of death and hospitalization.
Evolocumab is a monoclonal antibody designed to inhibit proprotein convertase subtillsin-kexin type 9 (PCSK9) and lower low-density lipoprotein (LDL) cholesterol levels to approximately 60%.
Until now, it was unclear whether the drug also helped lower cardiovascular events. In a study published in The New England Journal of Medicine, investigators found that evolocumab reduced the combined risk of heart attack, stroke, and cardiovascular-related death in patients with heart disease by 20%. The findings were presented at the American College of Cardiology annual conference.
The randomized, double-blind, placebo-controlled clinical trial included 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter. Participants were randomized to receive either 140 mg of evolocumab every 2 weeks, 420 mg of evolocumab monthly, or matching placebo as subcutaneous injections.
The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The secondary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years.
At 48 weeks, the results of the study showed that the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, compared with placebo, was 59% from a median baseline value of 92 mg per deciliter to 30 mg per deciliter.
Treatment with evolocumab significantly reduced the risk of primary endpoint compared with placebo (1344 patients vs 1563 patients, respectively), and the key secondary endpoint (816 vs 1013, respectively).
The findings remained consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels.
There were no significant differences in adverse events reported between the study groups, excluding injection-site reactions, which were more common with evolocumab.
“Inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events,” the authors concluded. “These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.”
Reviews of evolocumab have been mixed, with some physicians hailing the results as major progress against heart disease, while others expected more from the expensive drug.
“This [result] is probably a little less than we had been hoping for,” David Rind, MD, chief medical officer of the Institute for Clinical and Economic Review, told Kaiser Health News.
The price tag for evolocumab is $14,000 per year, while a generic statin costs only $250 per year.
Dr Steve Miller, senior vice president and chief medical officer at Express Scripts, said the high cost of evolocumab could place a financial burden on United States health system.
Cardiologist Cam Patterson, who was not involved in the study, also weighed in, telling KHN that due to the price of the drug, it would be unlikely that physicians would prescribe evolocumab for every patient with high cholesterol.
Despite the cost, Dr Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, believes evolocumab could be an important drug for high-risk patients.
“It would be hard for me to look a patient in the eye, if they’ve had a couple of heart attacks and is scared to death, and say it’s not worth you taking this medication,” Nissen said.