A similar uptick in treatment aggressiveness appeared in the ESC’s recommendations for managing very-high-risk patients in a primary prevention setting, including those without familial hypercholesterolemia. For these people, the ESC panel, which worked in concert with the European Atherosclerosis Society, pegged adding a PCSK9 inhibitor as a IIb (“may be considered”) recommendation when these very-high-risk people fail to reach their LDL-cholesterol target on a maximally tolerated statin and ezetimibe. Once again, this opening to use a PCSK9 inhibitor contrasted with the 2018 U.S. guideline, which never mentioned an option of adding a PCSK9 inhibitor for primary prevention except when someone also has familial hypercholesterolemia and starts treatment with an LDL level of at least 190 mg/dL (a IIb recommendation). The new European guidelines proposed using a PCSK9 inhibitor as a second-line option to consider when needed for people whose very high risk derives primarily from older age and other factors such as smoking or hypertension that give them at least a 10% 10-year risk for cardiovascular death as estimated with the European-oriented SCORE risk calculator tables.
Updated SCORE risk designations appear in the new ESC dyslipidemia guidelines, and they show, for example, that in lower-risk European countries (mostly Western European nations) virtually all men who are at least 70 years old would fall into the very-high-risk category that makes them potential candidates for treatment with a PCSK9 inhibitor regardless of any other risk they may or may not have. In higher-risk (mostly Eastern European) countries this designation kicks in for most men once they reach the age of 65.
Several Congress attendees who came to a discussion session on the guidelines voiced concerns that the new revision will lead to substantially increased use of the these drugs and hence will significantly boost medical costs, because these drugs today are priced at about $6,000 annually to treat one patient. In response, members of the guideline-writing panel defended their decision as unavoidable given what’s been reported on the clinical impact of PCSK9 inhibitors when lowering LDL cholesterol and cutting atherosclerotic cardiovascular disease events.
“I commend the [ESC] guideline for focusing on the science and on what is best for patients. The U.S. guidelines conflated the science and the cost, and the recommendations got watered down by cost considerations,” said Dr. Sabatine, who has led several studies of PCSK9 inhibitors.
Dr. Baigent added that the panel “deliberated long and hard on cost, but we felt that we had to focus on the evidence. The cost will shift” in the future, he predicted.
Other U.S. physicians highlighted the need to take drug cost into account when writing public health policy documents such as lipid-management guidelines and questioned whether this more liberal use of PCSK9 inhibitors was justified.
“I think that in the absence of familial hypercholesterolemia you need to waffle around the edges to justify a PCSK9 inhibitor,” said Dr. Eckel. “The cost of PCSK9 inhibitors has come down, but at $6,000 per year you can’t ignore their cost.”
“In the U.S. we need to be mindful of the cost of treatment,” said Dr. Stone. “The ESC guidelines are probably more aggressive” than the 2018 U.S. guideline. “They use PCSK9 inhibitors perhaps more than we do; we [in the United States] prefer generic ezetimibe. A lot has to do with the definitions of risk. The European guidelines have a lot of risk definitions that differ” from the U.S. guideline, he said.
Members of the ESC guidelines panel acknowledged that the SCORE risk-assessment charts could overestimate risk in older people who need primary prevention treatment, as well as underestimate the risk in younger adults.
This inherent age bias in the SCORE risk tables make it “extremely important to contextualize” a person’s risk “by considering other risk factors,” advised Brian A. Ference, MD, an interventional cardiologist and professor at Cambridge (England) University who was a member of the ESC guidelines writing group.
The new ESC guidelines say that risk categorization “must be interpreted in light of the clinician’s knowledge and experience, and of the patient’s pretest likelihood” of cardiovascular disease.”
Dr. Baigent has received research funding from Boehringer Ingelheim, Novartis, and Pfizer. Dr. Eckel has been an expert witness on behalf of Sanofi/Regeneron. Dr. Sabatine and Dr. Ference have received honoraria and research funding from several companies including those that market lipid-lowering drugs. Dr. Stone and Dr. Collins had no disclosures.
*Correction, 9/20/19: A previous version of this article incorrectly stated that the ESC guidelines were the first by a medical society to recommend the lower cholesterol goals. The American Association of Clinical Endocrinologists included targets below 55 mg/dL in their 2017 dyslipidemia management guidelines.
SOURCE: Mach F et al. Eur Heart J. 2019 Aug 31. doi: 10.1093/eurheartj/ehz455.