Perspective

Cholesterol guideline updated with newer medications, more personalized risk calculation

New recommendations from the American Heart Association, American College of Cardiology, American Diabetes Association and nine other societies advise a stepped approach to cholesterol management, including use of statins, ezetimibe and PCSK9 inhibitors for patients with prior cardiovascular disease at very high risk for another event.

“The most intensive LDL lowering is reserved for those patients at the very highest risk,” Neil J. Stone, MD, the Robert Bonow, MD, professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine and vice chair of the writing committee, said during a press conference at the American Heart Association (AHA) Scientific Sessions in November, where the new guidelines were unveiled.

The new guidance also calls for more personalized risk assessments than outlined in the previous version, which was published in 2013.

Of note, an LDL target of less than 70 mg/dL is recommended for certain high-risk patients. Targets had been eliminated in the 2013 guidelines.

“There is no ideal target for LDL in the general population, but in principle, lower is better,” AHA president Ivor Benjamin, MD, FAHA, director of the Cardiovascular Center at the Medical College of Wisconsin, said during the press conference.

Neil J. Stone

The guideline emphasizes management of cholesterol on a case-by-case basis and encourages patient-provider discussions of risk before deciding on a treatment plan.

“As we move into an era where care is personalized, how we prevent and treat heart disease differs patient by patient,” Richard Kovacs, MD, FACC, the Q.E. and Sally Russell Professor of Cardiology at Indiana University School of Medicine, clinical director of the Krannert Institute of Cardiology and vice president of the American College of Cardiology (ACC), said during the press conference. “These guidelines give us the tools we need to do that.”

The Pooled Cohort Equation from the 2013 guidelines remains as the recommended tool with which to estimate CVD risk.

“This is the most widely validated risk score in the contemporary U.S. population,” Stone said here. “The important point to remember is that the risk estimate should begin the risk discussion.”

10 take-home messages

The guideline, written by Scott M. Grundy, MD, PhD, FAHA, director of the Center for Human Nutrition, chairman of the department of clinical nutrition and director of the Clinical and Translational Research Center at UT Southwestern Medical Center, and colleagues, features 10 important take-home messages:

  • A lifetime of heart-healthy lifestyle should be emphasized for all patients.
  • Patients with clinical atherosclerotic CVD (ASCVD) should be prescribed a high-intensity statin or maximally tolerated statin therapy for LDL reduction.
  • Patients with ASCVD at very high risk, defined as multiple CVD events or one CVD event and multiple high-risk characteristics, should be considered for nonstatin therapy if statin therapy cannot achieve an LDL target of less than 70 mg/dL. Ezetimibe should be tried first; if the LDL target is still not achieved, after a cost discussion, a PCSK9 inhibitor may be considered.
  • Patients with LDL 190 mg/dL or more should be prescribed high-intensity statin therapy regardless of risk; high-risk patients with diabetes should be prescribed high-intensity statin therapy with a goal of reducing LDL by at least 50%.
  • In patients with diabetes aged 40 to 75 years with LDL at least 70 mg/dL, moderate-intensity statin therapy should be started regardless of 10-year ASCVD risk.
  • Richard Kovacs
  • Regarding adults aged 40 to 75 years being considered for statin therapy for primary prevention, a clinician-patient risk discussion should occur before commencing statin therapy. The discussion should include risk factors, risk-enhancing factors, potential benefits of lifestyle measures and statin therapy, potential for adverse events and drug-drug interactions, costs and patient preferences.
  • For adults without diabetes aged 40 to 75 years with LDL 70 mg/dL or higher, with 10-year ASCVD risk of at least 7.5%, a moderate-intensity statin regimen is recommended if the risk discussion favors it. If risk status is uncertain, coronary artery calcium (CAC) scoring can be used to improve specificity. If statin therapy is prescribed, the goal should be LDL reduction of at least 30% (at least 50% if 10-year atherosclerotic CVD risk is 20% or more).
  • For those with 10-year ASCVD risk of 7.5% to 19.9%, risk-enhancing factors can be used to further refine whether statin therapy should be initiated. Risk-enhancing factors include family history of premature ASCVD, persistent LDL of at least 160 mg/dL, metabolic syndrome, chronic kidney disease, preeclampsia, premature menopause, chronic inflammatory disorders, belonging to a high-risk race or ethnicity, persistent elevated triglycerides (at least 175 mg/dL), and, if measured, elevated apolipoprotein B, elevated high-sensitivity C-reactive protein, ankle-brachial index less than 0.9 and lipoprotein(a) 50 mg/dL or higher.
  • For those for whom risk-enhancing factors do not produce a refined risk assessment, consider measuring CAC. Statin therapy should be initiated in patients with CAC score 100 Agatston units or more, should be considered in patients with CAC score 1 to 99 Agatston units and should not be initiated in patients with a CAC score of 0 unless they are current smokers, have diabetes or have a family history of premature ASCVD.
  • After initiation of lipid-lowering therapies, assess adherence and response to medication and lifestyle measures at 4 to 12 weeks, then every 3 to 12 months thereafter.

The guideline has 26 class I recommendations, 29 class IIa recommendations, 14 class IIb recommendations and three class III recommendations, Sidney C. Smith Jr., MD, FAHA, FESC, FACP, MACC, professor of medicine at the University of North Carolina-Chapel Hill, past president of the AHA and the World Heart Federation and a member of the writing committee, said during the press conference.

“That is a lot to read, so I am telling people to know the class I and class III recommendations, then move on from there,” he said. “Understand that the guidelines are inclusive of the science we have learned in the last 5 years.” – by Erik Swain

Disclosures: All members of the writing committee, Benjamin and Kovacs report no relevant financial disclosures. Please see the guideline for a list of the reviewers’ relevant financial disclosures.

New recommendations from the American Heart Association, American College of Cardiology, American Diabetes Association and nine other societies advise a stepped approach to cholesterol management, including use of statins, ezetimibe and PCSK9 inhibitors for patients with prior cardiovascular disease at very high risk for another event.

“The most intensive LDL lowering is reserved for those patients at the very highest risk,” Neil J. Stone, MD, the Robert Bonow, MD, professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine and vice chair of the writing committee, said during a press conference at the American Heart Association (AHA) Scientific Sessions in November, where the new guidelines were unveiled.

The new guidance also calls for more personalized risk assessments than outlined in the previous version, which was published in 2013.

Of note, an LDL target of less than 70 mg/dL is recommended for certain high-risk patients. Targets had been eliminated in the 2013 guidelines.

“There is no ideal target for LDL in the general population, but in principle, lower is better,” AHA president Ivor Benjamin, MD, FAHA, director of the Cardiovascular Center at the Medical College of Wisconsin, said during the press conference.

Neil J. Stone

The guideline emphasizes management of cholesterol on a case-by-case basis and encourages patient-provider discussions of risk before deciding on a treatment plan.

“As we move into an era where care is personalized, how we prevent and treat heart disease differs patient by patient,” Richard Kovacs, MD, FACC, the Q.E. and Sally Russell Professor of Cardiology at Indiana University School of Medicine, clinical director of the Krannert Institute of Cardiology and vice president of the American College of Cardiology (ACC), said during the press conference. “These guidelines give us the tools we need to do that.”

The Pooled Cohort Equation from the 2013 guidelines remains as the recommended tool with which to estimate CVD risk.

“This is the most widely validated risk score in the contemporary U.S. population,” Stone said here. “The important point to remember is that the risk estimate should begin the risk discussion.”

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10 take-home messages

The guideline, written by Scott M. Grundy, MD, PhD, FAHA, director of the Center for Human Nutrition, chairman of the department of clinical nutrition and director of the Clinical and Translational Research Center at UT Southwestern Medical Center, and colleagues, features 10 important take-home messages:

  • A lifetime of heart-healthy lifestyle should be emphasized for all patients.
  • Patients with clinical atherosclerotic CVD (ASCVD) should be prescribed a high-intensity statin or maximally tolerated statin therapy for LDL reduction.
  • Patients with ASCVD at very high risk, defined as multiple CVD events or one CVD event and multiple high-risk characteristics, should be considered for nonstatin therapy if statin therapy cannot achieve an LDL target of less than 70 mg/dL. Ezetimibe should be tried first; if the LDL target is still not achieved, after a cost discussion, a PCSK9 inhibitor may be considered.
  • Patients with LDL 190 mg/dL or more should be prescribed high-intensity statin therapy regardless of risk; high-risk patients with diabetes should be prescribed high-intensity statin therapy with a goal of reducing LDL by at least 50%.
  • In patients with diabetes aged 40 to 75 years with LDL at least 70 mg/dL, moderate-intensity statin therapy should be started regardless of 10-year ASCVD risk.
  • Richard Kovacs
  • Regarding adults aged 40 to 75 years being considered for statin therapy for primary prevention, a clinician-patient risk discussion should occur before commencing statin therapy. The discussion should include risk factors, risk-enhancing factors, potential benefits of lifestyle measures and statin therapy, potential for adverse events and drug-drug interactions, costs and patient preferences.
  • For adults without diabetes aged 40 to 75 years with LDL 70 mg/dL or higher, with 10-year ASCVD risk of at least 7.5%, a moderate-intensity statin regimen is recommended if the risk discussion favors it. If risk status is uncertain, coronary artery calcium (CAC) scoring can be used to improve specificity. If statin therapy is prescribed, the goal should be LDL reduction of at least 30% (at least 50% if 10-year atherosclerotic CVD risk is 20% or more).
  • For those with 10-year ASCVD risk of 7.5% to 19.9%, risk-enhancing factors can be used to further refine whether statin therapy should be initiated. Risk-enhancing factors include family history of premature ASCVD, persistent LDL of at least 160 mg/dL, metabolic syndrome, chronic kidney disease, preeclampsia, premature menopause, chronic inflammatory disorders, belonging to a high-risk race or ethnicity, persistent elevated triglycerides (at least 175 mg/dL), and, if measured, elevated apolipoprotein B, elevated high-sensitivity C-reactive protein, ankle-brachial index less than 0.9 and lipoprotein(a) 50 mg/dL or higher.
  • For those for whom risk-enhancing factors do not produce a refined risk assessment, consider measuring CAC. Statin therapy should be initiated in patients with CAC score 100 Agatston units or more, should be considered in patients with CAC score 1 to 99 Agatston units and should not be initiated in patients with a CAC score of 0 unless they are current smokers, have diabetes or have a family history of premature ASCVD.
  • After initiation of lipid-lowering therapies, assess adherence and response to medication and lifestyle measures at 4 to 12 weeks, then every 3 to 12 months thereafter.
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The guideline has 26 class I recommendations, 29 class IIa recommendations, 14 class IIb recommendations and three class III recommendations, Sidney C. Smith Jr., MD, FAHA, FESC, FACP, MACC, professor of medicine at the University of North Carolina-Chapel Hill, past president of the AHA and the World Heart Federation and a member of the writing committee, said during the press conference.

“That is a lot to read, so I am telling people to know the class I and class III recommendations, then move on from there,” he said. “Understand that the guidelines are inclusive of the science we have learned in the last 5 years.” – by Erik Swain

Disclosures: All members of the writing committee, Benjamin and Kovacs report no relevant financial disclosures. Please see the guideline for a list of the reviewers’ relevant financial disclosures.

    Perspective
    Paul S.  Jellinger

    Paul S. Jellinger

    The updated cholesterol guidelines from ACC/AHA are a substantial improvement over the 2013 guidelines, and the new recommendations will certainly help many more patients and are a step forward for clinicians. This update filled in many gaps that were left in the 2013 guidelines. The emphasis on individualization of therapy and the expanded discussion of assessing risk, particularly with calcium scoring, is very useful. The re-focus on the threshold number of 70 mg/dL or higher will also benefit many patients. Embracing combination and PCSK9 therapy is clearly welcome.

    However, while these guidelines are much improved, they simply do not go far enough. The guidelines focus on thresholds when additional therapy should be considered and is reasonable and not on goals of treatment. Establishing thresholds for treatment is certainly useful, but after enhancing treatment, what is the goal of treatment? Patients whose LDL is close to 70 mg/dL would achieve, when appropriate, aggressively low LDL levels by add-on ezetimibe treatment to a maximally tolerated statin dose; however, those with an LDL of 120 mg/dL or higher would likely not without a PCSK9 inhibitor, which is indicated in these guidelines only for patients at very high risk. The data supporting lower is better is very strong and many patients benefit from very low LDL levels. Treatment goals could effectively be added to these recommendations. Most clinicians prefer goal-oriented guidelines, since they provide a focus to enhance treatment and are based on current LDL lower is better data. Finding the right number is difficult, but the IMPROVE-IT trial and the FOURIER prespecified outcome analysis of on-treatment LDL support an LDL goal for extreme risk patients of less than 55 mg/dL.

    Another valuable point worth noting: In the guidelines, major ASCVD events does not include coronary artery bypass grafting (CABG) or transient ischemic attack. The former is categorized under high risk conditions and the latter does not appear under either category. Most clinicians may well view CABG as a major atherosclerotic CVD event.

    The updated AACE guideline notes that adults with established CVD accompanied by type 2 diabetes, chronic kidney disease (stages 3 or 4) or familial hypercholesterolemia should be considered at extreme risk for atherosclerotic CVD, as should those with progressive CVD, including adults with unstable angina who have already achieved an LDL of 70 mg/dL. For these patients, an LDL cholesterol goal of less than 55 mg/dL is recommended. Such a target in this updated guideline would be useful, along with an effort to ensure that patients who are at extreme risk do not fall through the cracks.

    • Paul S. Jellinger, MD, MACE
    • Professor of Clinical Medicine
      University of Miami Miller School of Medicine
      The Center for Diabetes & Endocrine Care, Hollywood, Florida
      Past President, American Association of Clinical Endocrinologists
      Past President, American College of Endocrinology

    Disclosures: Jellinger reports he has received speaking fees from Amgen, Astra Zeneca, Janssen, Merck, Novo Nordisk and Regeneron and serves on advisory boards for Amgen and Regeneron.

    Perspective
    Steven E. Nissen

    Steven E. Nissen

    The 2013 guidelines received a lot of criticism. The new guidelines have addressed many of those concerns correctly and appropriately. The authors are bringing back the idea of LDL targets; you should not just give a statin and walk away. They are recommending more aggressive treatment of patients with LDL greater than 70 mg/dL, using add-ons of nonstatin therapies, such as ezetimibe and PCSK9 inhibitors, if necessary. That is a big step forward. Many of us have believed for quite some time that lower is better. The guidelines now acknowledge that.

    There is also a renewed emphasis on monitoring LDL levels, which was not suggested in the 2013 guidelines. Now, periodic measurement and adjustment of therapy is recommended. That is very reasonable.

    A tough issue for the committee to acknowledge is that the risk calculator works for populations, but not necessarily for individuals. Emphasis on it has been greatly softened, and the committee is recommending use of additional factors, which some of us advocated for in 2013. These factors include family history, C-reactive protein and calcium scanning, which are not in the risk calculator. There is acknowledgement that the risk calculator is an imperfect tool that may be miscalibrated in some people, either overestimating or underestimating their risk.

    The committee also acknowledged that the previous guidelines may have been in error by not recommending treatment in patients over age 75 years. The new guidelines recommend considering treatment in patients over 75 if they are at appropriately high risk. I agree with that. The document also recommends more aggressive treatment of young patients with diabetes, which I also agree with.

    The only thing that I am in strong disagreement with is the advocacy for calcium scanning. I do not think it is prudent to expose people to ionizing radiation using a test that costs $800 to $1,000 in order to determine whether to use a drug that costs as little as $3 per month. It does not make good public health sense.

    • Steven E. Nissen, MD, MACC
    • Chairman, Department of Cardiovascular Medicine Cleveland Clinic Professor of Medicine Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

    Disclosures: Disclosure: Nissen reports no relevant financial disclosures.