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European cholesterol guidelines push LDL targets below 55 mg/dL

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A welcome addition for managing lipid disorders
Paul S. Jellinger, MD

The new ESC dyslipidemia guidelines recently presented at the society’s annual congress are a welcome addition to the lipid disorder treatment guidelines available to clinicians. These guidelines follow the groundbreaking recommendation in 2017 by AACE in their updated guidelines that introduced an LDL goal of <55 mg/dL in “extreme risk” patients. The ESC guidelines now also recommend an LDL goal of <55 mg/dL in “very-high-risk” patients but go further by also requiring a 50% reduction in LDL. Furthermore, they have established an LDL goal of <40 mg/dL in patients who experienced a second vascular event in the past 2 years while on maximally tolerated statin dose.

The ESC very-high-risk category shares many features with AACE’s extreme-risk category but is broader in that it includes patients without a clinical event who display unequivocal evidence of arteriosclerotic cardiovascular disease (ASCVD) on imaging and patients with severe chronic kidney disease (GFR <30 mL/min ) without known ASCVD. There are substantial differences between the ESC and AHA-ACC 2018 guidelines in the very-high-risk category. The AHA very-high-risk is directed toward secondary prevention only and requires two major ASCVD events or one major and at least two high-risk conditions. Moreover, elements of both major ASCVD events and high-risk conditions as well as the very-high-risk eligibility requirements could mean that some patients, who would clearly be classified by both ESC and AACE as candidates for an LDL goal of <55, may not qualify for threshold consideration for maximal LDL lowering below 70 mg/dL including the use of PCSK9 inhibitors. Relative to this point, the AHA-ACC guidelines do not classify past CABG or PCI as a major ASCVD event, nor is a TIA considered a major event or a high-risk condition.

For LDL, “lower is better” is supported by years of statin clinical trial evidence, along with the robust findings in the 2010 Cholesterol Trialists Collaboration. The goal of <55 mg/dL is supported by the IMPROVE-IT, FOURIER, and ODYSSEY trials. The ESC guidelines appropriately take this body of evidence and applies it to an aggressive treatment platform that, like AACE, sets clinically useful LDL goals for clinicians and patients. It takes early, aggressive LDL-lowering treatment to stay ahead of atherosclerotic plaque development in patients who are at very high or extreme risk. Following AACE’s lead, the ESC guidelines are the newest tool available to clinicians addressing this issue with the promise of further decreasing CVD events and extending lives.

Dr. Jellinger is a member of the editorial advisory board for Clinical Endocrinology News. He is professor of clinical medicine on the voluntary faculty at the University of Miami Miller School of Medicine and a practicing endocrinologist at The Center for Diabetes & Endocrine Care in Hollywood, Fla. He is past president of the American Association of Clinical Endocrinologists and the American College of Endocrinology and was chair of the writing committee for the 2017 AACE-ACE lipid guidelines.


 

REPORTING FROM THE ESC CONGRESS 2019

– The 2019 dyslipidemia management guidelines from the European Society of Cardiology set an LDL cholesterol target for very-high-risk people of less than 55 mg/dL (as well as at least a 50% cut from baseline), a class I recommendation. This marks the first time a cardiology society has either recommended a target goal for this measure below 70 mg/dL or endorsed treating patients to still-lower cholesterol once their level was already under 70 mg/dL.*

The guidelines went further by suggesting consideration of an even lower treatment target for LDL-cholesterol in very-high-risk, secondary prevention patients who have already had at least two atherosclerotic cardiovascular disease events during the past 2 years, a setting that could justify an LDL-cholesterol goal of less than 40 mg/dL (along with a cut from baseline of at least 50%), a class IIb recommendation that denotes a “may be considered,” endorsement.

“In all the trials, lower was better. There was no lower level of LDL cholesterol that’s been studied that was not better” for patient outcomes, Colin Baigent, BMBCH, said while presenting the new guideline at the annual congress of the European Society of Cardiology (ESC). “It’s very clear” that the full treatment benefit from lowering LDL-cholesterol extends to getting very-high risk patients below these levels, said Dr. Baigent, professor of cardiology at Oxford (England) University and one of three chairs of the ESC’s dyslipidemia guideline-writing panel.

While this change was seen as a notably aggressive goal and too fixed on a specific number by at least one author of the 2018 American Heart Association/American College of Cardiology cholesterol management guideline (J Am Coll Cardiol. 2019 Jun;73[24]:e285-e350), it was embraced by another U.S. expert not involved in writing the most recent U.S. recommendations.

Dr. Robert H. Eckel, University of Colorado, Aurora

Dr. Robert H. Eckel

“A goal for LDL-cholesterol of less than 55 mg/dL is reasonable; it’s well documented” by trial evidence “and I support it,” said Robert H. Eckel, MD, an endocrinologist and professor of medicine at the University of Colorado in Aurora. Dr. Eckel added that he “also supports” an LDL-cholesterol of less than 40 mg/dL in very-high-risk patients with a history of multiple events or with multiple residual risk factors, and he said he has applied this lower LDL-cholesterol goal in his practice for selected patients. But Dr. Eckel acknowledged in an interview that the evidence for it was less clear-cut than was the evidence behind a goal of less than 55 mg/dL. He also supported the concept of including a treatment goal in U.S. lipid recommendations, which in recent versions has been missing. “I fall back on a cholesterol goal for practical purposes” of making the success of cholesterol-lowering treatment easier to track.

The new ESC goal was characterized as “arbitrary” by Neil J. Stone, MD, vice-chair of the panel that wrote the 2018 AHA/ACC guideline, which relied on treating secondary-prevention patients at high risk to an LDL-cholesterol at least 50% less than before treatment, and recommended continued intensification for patients whose LDL-cholesterol level remained at or above 70 mg/dL.

Dr. Neil J. Stone, Northwestern University, Chicago

Dr. Neil J. Stone

“If the patient is at 58 mg/dL I’m not sure anyone can tell me what the difference is,” compared with reaching less than 55 mg/dL, Dr. Stone said in an interview. “I worry about focusing on a number and not on the concept that people at the very highest risk deserve the most intensive treatment; the Europeans agree, but they have a different way of looking at it. Despite this difference in approach, the new ESC guidelines and the 2018 U.S. guideline “are more similar than different,” stressed Dr. Stone, professor of medicine and preventive medicine at Northwestern University, Chicago.

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