AACE Issues 'Cookbook' Algorithm to Manage Dyslipidemia

Dr Yehuda Handelsman

A new algorithm on lipid management and prevention of cardiovascular disease from the American Association of Clinical Endocrinologists* (AACE) and the American College of Endocrinology (ACE) is "a nice cookbook" that many clinicians, especially those who are not lipid experts, will find useful, according to writing committee chair Yehuda Handelsman, MD.

The algorithm, published Oct. 10 in Endocrine Practice as 10 slides, or as part of a more detailed consensus statement, is a companion to the 2017 AACE/ACE guidelines for lipid management and includes more recent information about new therapies.

"What we're trying to do here is to say, 'focus on LDL-C, triglycerides, high-risk patients, and lifestyle. Understand all the medications available to you to reduce LDL-C and reduce triglycerides,' " Handelsman, of the Metabolic Institute of America, Tarzana, Calif., explained in an interview.

"We touch on lipoprotein(a), which we still don't have medication for, but it identifies people at high risk, and we need that."

Clinicians also need to know "that we've got some newer drugs in the market that can manage people who have statin intolerance," Handelsman added.

"We introduced new therapies like icosapent ethyl" (Vascepa, Amarin) for hypertriglyceridemia, "when to use it, and how to use it. Even though it was not part of the 2017 guideline, we gave recommendations based on current data in the algorithm."

Dr Robert H. Eckel

Although there is no good evidence that lowering triglycerides reduces heart disease, he continued, many experts believe that the target triglyceride level should be less than 150 mg/dL, and the algorithm explains how to treat to this goal.

"Last, and most importantly, I cannot fail to underscore the fact that lifestyle is very important," he emphasized.

Robert H. Eckel, MD, of the University of Colorado at Denver, Aurora, and president of medicine and science at the American Diabetes Association, who was not involved with this algorithm, said in an interview that the algorithm is important since it offers "the clinician or health care practitioner an approach, a kind of a cookbook or application of the guidelines, for how to manage lipid disorders in patients at risk ... It's geared for the nonexperts too," he said.

Dyslipidemia Treatment Summarized in 10 Slides

The AACE/ACE algorithm comprises 10 slides, one each for dyslipidemic states, secondary causes of lipid disorders, screening for and assessing lipid disorders and atherosclerotic CVD (ASCVD) risk, ASCVD risk categories and treatment goals, lifestyle recommendations, treating LDL-C to goal, managing statin intolerance and safety, management of hypertriglyceridemia and the role of icosapent ethyl, assessment and management of elevated lipoprotein(a), and profiles of medications for dyslipidemia.

The algorithm defines five ASCVD risk categories and recommends increasingly lower LDL-C, non–HDL-C, and apo B target levels with increasing risk, but the same triglyceride target for all.

First, "treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids," the consensus statement authors stress.

Next, "LDL-C has been, and remains, the main focus of efforts to improve lipid profiles in individuals at risk for ASCVD (see Table)."

Table. ACSVD risk categories and LDL-C treatment targets

ASCVD risk	Patient characteristics	LDL-C goal (mg/dL)
Extreme	Progressive ASCVD, including unstable angina Established clinical ASCVD plus diabetes or stage 3-5 CKD or heterozygous familial hypercholesterolemia Premature ASCVD (age < 55 years, male; < 65 years, female)	< 55
Very high	Established clinical ASCVD (or recent hospitalization for coronary, carotid, or peripheral vascular disease) with 10-year risk > 20% Diabetes with one or more risk factors* Stage 3-5 CKD with albuminuria Heterozygous familial hypercholesterolemia	< 70
High	Two or more risk factors* and 10-year risk of 10% to 20% Diabetes or stage 3-5 CKD with no other risk factors*	< 100
Moderate	Two or more risk factors* and 10-year risk of 10% to 20% Diabetes or stage 3-5 CKD with no other risk factors*	< 100
Low	No risk factors*	< 130

*Risk factors = advancing age, elevated non-HDL-C, elevated LDL-C, low HDL-C, diabetes, hypertension, CKD, cigarette smoking, and family history of ASCVD

"We stratify [LDL-C] not as a one-treatment-target-for-all," but rather as extreme, very high, high, moderate, and low ASCVD risk, Handelsman explained, with different treatment pathways (specified in another slide) to reach different risk-dependent goals.

"Unlike the ACC [American College of Cardiology] guideline, which shows if you want to further reduce LDL after statin give ezetimibe first, we say 'no'," he noted. "If somebody has an extreme risk, and you don't think ezetimibe will get to a goal below 55 mg/dL, you should go first with a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor, and only then add ezetimibe or [colesevelam] or other drugs," he said.

The consensus statement authors expand on this scenario. "Treatment for patients at extreme risk should begin with lifestyle therapy plus a high-intensity statin (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg, or the highest tolerated statin dose) to achieve an LDL-C goal of less than 55 mg/dL."

"If LDL-C remains above goal after 3 months," a PCSK9 inhibitor (evolocumab [Repatha, Amgen] or alirocumab [Praluent, Sanofi/Regeneron]), the cholesterol absorption inhibitor ezetimibe, or the bile acid sequestrant colesevelam (Welchol, Daiichi Sankyo) or the adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid (Nexletol, Esperion) "should be added, depending on required LDL-C lowering, and a third agent should be added if the combination fails to achieve the goal."

However, "because the cost of ezetimibe is low, it may be preferred over PCSK9 inhibitors as second-line therapy to achieve an LDL-C below 70 mg/dL for patients who require no more than 15%-20% further reduction to reach goals."

For patients at moderate or high risk, lipid management should begin with a moderate-intensity statin and be increased to a high-intensity statin before adding a second lipid-lowering medication to reach an LDL-C below 100 mg/dL.

According to the consensus statement, the desirable goal for triglycerides is less than 150 mg/dL.

In all patients with triglyceride levels of at least 500 mg/dL, statin therapy should be combined with a fibrate, prescription-grade omega-3 fatty acid, and/or niacin to reduce triglycerides.

In any patient with established ASCVD or diabetes with at least 2 ASCVD risk factors and triglycerides of 135-499 mg/dL, icosapent ethyl should be added to a statin to prevent ASCVD events.

Statement Aligns With Major Guidelines

In general, the 2017 AACE/ACE guidelines and algorithm are "pretty similar" to other guidelines such as the 2018 ACC/American Heart Association (AHA) guidelines for cholesterol management, the 2019 ACC/AHA guidelines for primary prevention of CVD, and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidemia, according to Eckel.

They have "all have now taken into consideration the evidence behind PCSK9 inhibitors," he noted. "That's important because those drugs have proven to be effective."

Two differences, he pointed out, are that the 2019 ESC/EAS guidelines suggest that lipoprotein(a) measurement be considered at least once in every adult's lifetime, and they recommend apo B analysis in people with high triglycerides but normal LDL (or no higher than 100 mg/dL), to identify additional risk.

*AACE Changes its Name, Broadens Focus

Shortly after its algorithm was published, AACE announced that it has a new organization name and brand, the American Association of Clinical Endocrinology, which "more clearly defines AACE as a community of individuals who work together to elevate the practice of clinical endocrinology," according to an Oct. 20 statement.

The change is meant to acknowledge AACE's "more modern, inclusive approach to endocrinology that supports multidisciplinary care teams – with endocrinologists leading the way."

Along with the name change is a new global website. The statement notes that "health care professionals and community members can access all of the valuable clinical content such as guidelines, disease state networks and important education by visiting the pro portal in the top right corner of the site, or by going directly to pro.aace.com."

Handelsman discloses that he receives research grant support from Amgen, Applied Therapeutics, AstraZeneca, BMS, Gan & Lee, Novo Nordisk, and Sanofi, and he is a consultant and/or speaker for Amarin, BI-Lilly, and Sanofi.

Eckel has received consultant/advisory board fees from Kowa, Novo Nordisk, and Provention Bio.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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