Adding Evolocumab to a Statin May Benefit Some High-Risk Patients

11/13/17

By Marilynn Larkin

NEW YORK (Reuters Health) – Adding evolocumab to statin therapy in high-risk patients with stable atherosclerotic heart disease may further reduce the risk of cardiovascular events, regardless of low-density lipoprotein (LDL) cholesterol level, researchers say.

Current guidelines endorse an LDL cholesterol level <70 mg/dL or a threshold for treatment of at least 70 mg/dL to prevent secondary cardiovascular events in patients at highest risk, according to Dr. Robert Giugliano of Brigham and Women’s Hospital in Boston and colleagues.

Whether reducing LDL levels further would benefit patients who already are below 70 mg/dL and are taking maximum-potency statins is unknown, they add.

To see whether adding evolocumab makes a difference in these patients’ outcomes, the team conducted a secondary analysis of data from the FOURIER trial, which had compared various treatments in patients with stable heart disease, classified at baseline by LDL levels and by statin intensity (http://bit.ly/2n9Ej1L).

As reported online November 8 in JAMA Cardiology, the analysis included 27,564 patients (mean age, 62.5; 75% men).

Among the 2,034 patients (7.4%) whose baseline LDL level was <70 mg/dL, adding evolocumab reduced the risk for the primary endpoint – a composite of cardiovascular death, heart attack, stroke, hospitalization for unstable angina or coronary revascularization - to a similar degree as in the 25,529 patients with a baseline LDL level of at least 70 mg/dL.

Of the 7,533 patients (27.3%) receiving maximal-potency statins, evolocumab significantly reduced the primary endpoint to a similar degree as in the 20,031 patients not receiving a maximal-potency statin.

Results were consistent for the key secondary endpoint – a composite of cardiovascular death, heart attack or stroke. There were no major safety concerns.

“The bottom line is that clinicians who have high-risk patients (e.g., previous heart attack or stroke and current risk factors) and who can’t get the LDL down to the level they want, evolocumab is an excellent option,” Dr. Giugliano told Reuters Health.

What about lifestyle changes?

“All these patients were advised to make lifestyle changes and were given appropriate education,” Dr. Giugliano said by phone. “But modifying LDL by lifestyle will get perhaps a 10% reduction, and we’re looking to get reductions of 50% or greater.”

Is adding evolocumab to a statin cost-effective? “That depends on your budget and your risk threshold, but for high-risk patients who have a higher probability of heart attack, it has been shown to be cost-effective,” Dr. Giugliano said. “For low-risk patients, it will be very costly.”

Future research will address other patient populations, including those at low risk of cardiovascular events, and other ways to deliver the drug – “hopefully, orally,” he concluded.

Like Dr. Giugliano, Dr. David Waters of the University of California, San Francisco, author of an accompanying editorial, told Reuters Health, “For most patients, lifestyle changes do not have a large effect on cholesterol levels. Drugs do.”

Is polypharmacy a concern?

“Polypharmacy is a concern,” Dr. Waters affirmed by email. “Nobody likes to take 14 different drugs each day.”

“On the other hand, approximately 80% of those who are at high risk will die from cardiovascular disease, and polypharmacy (statin, ACE inhibitor, platelet inhibitors, plus beta-blocker) will reduce that risk by more than half,” he observed.

He concluded, “In high-risk subjects, non-compliance with lifesaving medication is a bigger issue than polypharmacy.”

Amgen, maker of evolocumab, sponsored the original (FOURIER) trial. Dr. Giugliano and eight coauthors have received funds from Amgen, and one author is an employee and stockholder of the company.

SOURCES: http://bit.ly/2AqNdNN and http://bit.ly/2zw3010

JAMA Cardiol 2017.

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