AACE, ACE Dyslipidemia Clinical Practice Guidelines Update

The executive summary of the guidelines 87 evidence-based recommendations that allow for nuance-based clinical decision-making.


1- l'identificazione di una categora ulteriore di rischio cardiovascolare: rischio ESTREMO: malattia cardiovascolare progressiva, angina instabile, pazienti con cardiopatia e diabete o insufficienza renale o iperCT familiare; in cui è indicato raggiungere licelli di LDL meno di 55
2- l'ulteriore riduzione del CT-LDL e del rischio cardiovascolare aggiungendo l'ezetimibe (ezetrol, zetia, ed altri) alle statine

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) are ushering in a new era with the 2017 clinical practice guidelines for dyslipidemia management and atherosclerosis prevention. The guidelines, which have just been released online, include a new cardiovascular risk category.The guidelines also address a broader range of disease stages and call for more intense treatment and more aggressive intervention.


The executive summary contains 87 evidence-based recommendations that allow for nuance-based clinical decision-making. The clinical practice guidelines are intended to be a practical tool for endocrinologists to employ as a means of reducing the risks and consequences of dyslipidemia.

The new guidelines call for treating low-density lipoprotein cholesterol (LDL-C) levels in specific patient groups to lower goals than previously recommended. They also support the use of coronary artery calcium scores and inflammatory markers to help clinicians better stratify risk. Another notable feature is that the guidelines call for special consideration when it comes to patients with diabetes or familial hypercholesterolemia, women, and pediatric patients with dyslipidemia.

Extreme Risk Category

The Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Dyslipidemia and Prevention of Atherosclerosis were published by AACE in 2012. The 2017 update introduces a cardiovascular disease "Extreme Risk" category. The Extreme Risk category includes patients who have progressive cardiovascular disease, such as patients with unstable angina who have achieved a lowered LDL-C level and patients who have established cardiovascular disease accompanied by diabetes mellitus, chronic kidney disease (stages 3 or 4), or familial hypercholesterolemia.

The Extreme Risk category also includes men aged 55 years and younger and women aged 65 years and younger who have a history of premature cardiovascular disease.

"The Extreme Risk category with an LDL-C goal of <55 mg/dL is groundbreaking and represents the first time an organization has recommended this degree of LDL reduction. Much evidence has been pointing in this direction, but no recommendation until now had been made," Paul Jellinger, MD, chairman of the AACE Lipids Guidelines Update Task Force Writing Committee, told Endocrinology Advisor.

He said data from the IMPROVE-IT trial (ClinicalTrials.gov identifier:NCT00202878) helped lead to some of the changes in the new guidelines. This trial showed that the addition of a nonstatin agent (ezetimibe) to a statin therapy lowered LDL-C by approximately 24%.2 The study also demonstrated that combining simvastatin and ezetimibe, which reduces the absorption of cholesterol from the gastrointestinal tract, resulted in a significantly lower risk for cardiovascular events than that seen with statin monotherapy.

Dr Jellinger, who is a past president of ACE, said the IMPROVE-IT trial confirmed what had been observed in previous clinical trials. "Prior outcome studies revealed that those patients treated with statins achieving the lowest LDL-C values had the best outcomes," Dr Jellinger told Endocrinology Advisor.

"IMPROVE-IT was designed to test whether lowering LDL further beyond aggressive statin therapy with ezetimibe would improve outcomes. With statin plus ezetimibe, an average LDL-C of 53 mg/dL was achieved compared to the statin-alone group LDL-C of 69.9 mg/dL."

He said there were also significant reductions in the atherosclerotic cardiovascular disease (ASCVD) end points in the statin-plus-ezetimibe group. Dr Jellinger said this "lower-is-better" benefit has been further demonstrated in several large meta-analyses.3, 4

The guidelines emphasize the importance of assessing women for cardiovascular disease using instruments that determine the 10-year risk for a coronary event. They also call for diagnosing and managing children and adolescents with dyslipidemia as early as possible to try to decrease the long-term risk for an adult cardiovascular event. The guidelines are designed to improve cardiovascular disease detection and supply the necessary support for clinicians for optimal disease management.

Dr Jellinger noted that this year's update is important to endocrinologists and their patients. It is hoped that outcomes will improve in the coming months and years as these changes are incorporated into clinical practice. "The Extreme Risk category includes patients with diabetes mellitus and cardiovascular disease. Endocrinologists see such patients every day. Until now, their LDL-C goal was <70 mg/dL. Now, it is <55 mg/dL," he said.

MacRae Linton, MD, professor of medicine from the Atherosclerosis Research Unit at Vanderbilt University School of Medicine, Nashville, Tennessee, said there are several important new aspects of care that may be of particular concern to endocrinologists, including the emphasis on patients with metabolic syndrome, type 2 diabetes, and type 1 diabetes at high risk for cardiovascular disease.

"These are true clinical practice guidelines based on an enormous amount of clinical evidence that empower the practitioner to aggressively manage dyslipidemia in patients at risk [for cardiovascular disease]. The inclusion of targets for LDL, non-HDL, and [apolipoprotein] B100 is an important feature and is based on clinical trial evidence showing that lower is better in high-risk patients," Dr Linton told Endocrinology Advisor.

The creation of an Extreme Risk category further supports the need for more aggressive LDL and non-HDL lowering in individuals with progressive ASCVD, established ASCVD and diabetes, stage 3 or 4 chronic kidney disease, or heterozygous familial hypercholesterolemia, as well as those with a history of premature ASCVD.

"The inclusion of non-HDL goals is particularly important for management of individuals with hypertriglyceridemia, a problem that is common in metabolic syndrome and diabetes. There is also an increased emphasis on management of dyslipidemia in children," Dr Linton noted.

Summary and Clinical Applicability

Familial hypercholesterolemia is a common inherited cause of severely elevated levels of LDL-C and increased risk for premature cardiovascular disease that is underdiagnosed and undertreated in the United States, according to Dr Linton. It is theorized that improved diagnosis and treatment of familial hypercholesterolemia in children should lead to a reduction in premature heart attacks and death.

"The creation of an Extreme Risk category with a more aggressive LDL-C goal of <55 mg/dL may be viewed as unexpected and is potentially important. With the advent of [proprotein convertase subtilisin/kexin type 9 (PCSK9)] inhibitors, we now have the ability to achieve lower levels of LDL-C than in the past. The results of the ongoing outcomes studies with PCSK9 inhibitors will be important in terms of providing evidence as to whether combination therapy with a statin that is capable of achieving very low levels of LDL-C will significantly reduce cardiovascular events," Dr Linton concluded.

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