By AMERICAN HEART ASSOCIATION NEWS
A highly anticipated study has found that the new cholesterol-lowering drug evolocumab can reduce heart attacks and strokes among high-risk patients.
The findings, published last week in the New England Journal of Medicine and presented at the American College of Cardiology’s annual meeting, showed that the drug, when added to intensive statin therapy, cut the risk of having a heart attack, stroke or dying from a cardiovascular cause by 20 percent.
The study was paid for by Amgen, which makes and sells the drug under the brand name Repatha.
“There have been studies of PCSK9 inhibitors during the past several years … [and] this study is important because it’s the first to show needed evidence that a dramatic reduction of LDL cholesterol is associated with reduction in heart attack and stroke,” said former American Heart Association President Sidney C. Smith Jr., M.D., of the University of North Carolina at Chapel Hill. Smith, who was not involved in the study, co-authored AHA’s 2013 cholesterol guidelines.
In the study, Repatha lowered “bad” LDL cholesterol by about 60 percent to a median of 30.
“When added to intensive statin therapy, the drug results in an impressive reduction in LDL cholesterol in high-risk patients with cardiovascular disease,” Smith said.
Repatha inhibits PCSK9, a protein that affects the body’s ability to remove LDL from the bloodstream. The Food and Drug Administration approved the injectable drug in 2015 for people with very high LDL due to inherited conditions and those with persistently high LDL who have a history of heart attack, stroke or other heart problems.
High cholesterol is a risk factor for heart disease and stroke, the world’s top two killers. Current guidelines recommend statin treatment for adults at high risk of heart attacks and strokes.
The study, called FOURIER, followed 27,564 people for an average of 2.2 years. All the participants had heart disease and LDL cholesterol levels of 70 or higher and were already taking intensive statin therapy.
In the Repatha group, 5.9 percent had a heart attack, stroke or died from cardiovascular disease, compared with 7.4 percent in the placebo group. The benefit grew with longer use of the drug, reducing risk by 25 percent after the first year, said the study’s lead researcher, Marc S. Sabatine, M.D., of Brigham and Women’s Hospital in Boston.
“We now have evidence that adding evolocumab to statins can significantly reduce the risk of heart attack and stroke,” he said.
When researchers expanded the criteria to include the problems above plus patients hospitalized for chest pain or who needed a stent to open a blocked artery, the reduction in risk was 15 percent, with 9.8 percent of patients taking Repatha having one of the outcomes, compared with 11.3 percent of those taking the placebo.
“An important corollary is that we need to be treating LDL cholesterol even more vigorously,” Sabatine said. “We’ve been marching down the line of lowering LDL cholesterol levels, and now we’ve taken another significant step lower.”
While the results offer promise for high-risk patients who don’t respond well to statins or diet changes, the trial was relatively short, Smith said. “In my opinion, we’d like to see further data, out as far as at least four years,” he said.
Another potential roadblock is Repatha’s high price, which could affect insurance companies’ decision to pay for the drug. A separate study presented at the ACC conference found that about 80 percent of prescription claims for the two PCSK9 inhibitor drugs on the market were initially rejected by insurers. More than half of those claims were eventually denied.
“The medication is expensive, costing [more than] $14,000 a year,” Smith said, adding that insurance companies might ultimately see the drug as cost-effective.
“The first step is having the science and the clinical outcomes to show that patients benefit significantly. An insurance company will be motivated, among other factors, by the potential decrease of hospitalization,” Smith said. “Demand from patients and physicians can also affect funding decisions … . There might be some way to negotiate lower costs if large numbers of patients were to be treated.”
Sabatine said, “Given the new outcomes data, I hope this will translate into a less burdensome process for patients to get these drugs.”
Smith said the ultimate price of Repatha and other PCSK9 inhibitor drugs could hinge on the results of the longer ODYSSEY Outcomes trial of Praluent (alirocumab), a PCSK9 inhibitor also approved in 2015. The study is scheduled for completion within the next year.
“The combination of ODYSSEY, with favorable results, and FOURIER would provide strong information,” Smith said. “The combination of the two could provide the motivation and the needed evidence to get beyond the concerns about cost.”