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ROME -- Are PSCK9 inhibitors ready for widespread use, or should a major roll-out of the high priced cholesterol-lowering agents be put on hold until definitive outcome studies are done?

A packed audience at a debate session at the European Society of Cardiology annual meeting heard the argument made by , that PSCK9 inhibitors are needed now for patients with genetic disorders, and those who were unable to tolerate statins. Navarese is with the INOVA Center for Thrombosis Research and Drug Development, INOVA Health Care in Falls Church, Va.

PCSK9 inhibitors are monoclonal antibodies that target and inactivate the protein, proprotein convertase subtilisin kexin 9, in the liver, reducing the amount of LDL cholesterol circulating in the bloodstream. The FDA has approved two PCSK9 inhibitors: Alirocumab (Praluent) and evolocumab (Repatha).

Statins are the "cornerstone of lipid modification," Navarese acknowledged, but patients who cannot achieve ideal LDL cholesterol goals on these agents are still at significant cardiovascular risk.

Higher reduction of LDL cholesterol is tied to improved clinical outcomes, he added.

"PSCK9 inhibitors currently fill a therapeutic niche, which include patients with high cardiovascular risk such as familial hypercholesterolemia; clinical atherosclerotic disease; or statin-intolerant patients who are not able to achieve the desired LDL cholesterol level," he said.

But given the cost of PSCK9 drugs, more data on outcomes and side effects are needed, argued at the University of Oslo.

Pedersen noted that several trials are underway that compare PSCK9 inhibitors to standard-of-care statin drugs. He presented cost data showing that a year's prescription for atorvastatin (Lipitor) or simvastatin (Zocor) in Norway was about $225, while the cost for evolocumab (Repatha) was about $8,517 a year, while the cost for alirocumab was about $8,443 a year.

He said the cost of treating the patients cited by Navarese would range from $12 billion to $54 billion a year.

He also contended that most patients on statins who fail to reach treatment goals are generally those who refuse medication or are nonadherent. Even if the take their statins and don't reach certain goals, they are closer enough so that the potent PSCK9 inhibitors would be akin to excessive treatment, he said.

"Patients who should be considered for PSCK9 inhibitors are those patients with familial hypercholesterolemia with intact LDL-receptors on plasmapheresis, or patients with [familial] hypercholesterolemia with LDL-cholesterol far above current guideline limits, despite optimal treatment with statins and ezetimibe [Zetia]," Pedersen said.

After long-term trials and cost-effectiveness analyses are performed, reconsideration of those who should be treated would be warranted, he acknowledged.

Debate co-moderator , of the Academic Teaching Hospital in Feldkirch, Austria, stated that PSCK9 inhibitors "promising, but are not proven."

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