Meeting NewsPerspective

Cholesterol guidelines updated with newer medications, more personalized risk calculation

Neil J. Stone

CHICAGO — New cholesterol guidelines from the American Heart Association, American College of Cardiology and 10 other societies recommend a stepped approach including statins, ezetimibe and PCSK9 inhibitors in patients with prior CVD 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 AHA Scientific Sessions, where the new guidelines were unveiled.

Personalized risk assessment, LDL targets

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 < 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.

The guidelines emphasize management of cholesterol on a case-by-case basis and encourage patient-provider discussions of risk before a decision on a treatment plan.

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New cholesterol guidelines from the American Heart Association, American College of Cardiology and 10 other societies recommend a stepped approach including statins, ezetimibe and PCSK9 inhibitors in patients with prior CVD at very high risk for another event.
Source: Adobe Stock

“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 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 guidelines, 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, feature 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 they cannot achieve an LDL target of < 70 mg/dL on statin therapy. 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%.
  • 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.
  • In patients aged 40 to 75 years with diabetes and LDL at least 70 mg/dL, moderate-intensity statin therapy should be started regardless of 10-year ASCVD risk.
  • For adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and 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 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 adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and 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 < 0.9 and lipoprotein(a) 50 mg/dL or higher.
  • For adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and with 10-year ASCVD risk of 7.5% to 19.9%, if 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 atherosclerotic CVD.

“A CAC score of 0 means the 10-year event rates are likely to be below the range where statins provide a net benefit,” Stone said at the press conference.

  • 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 guidelines have 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.”

Sidney C. Smith Jr.

The guidelines were simultaneously published in Circulation and the Journal of the American College of Cardiology. – by Erik Swain

References:

Grundy SM, et al. 2018 AHA/ACC Cholesterol Clinical Practice Guidelines. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

Grundy SM, et al. Circulation. 2018;doi:10.1161/CIR.0000000000000625.

Grundy SM, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.11.002.

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

Neil J. Stone

CHICAGO — New cholesterol guidelines from the American Heart Association, American College of Cardiology and 10 other societies recommend a stepped approach including statins, ezetimibe and PCSK9 inhibitors in patients with prior CVD 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 AHA Scientific Sessions, where the new guidelines were unveiled.

Personalized risk assessment, LDL targets

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 < 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.

The guidelines emphasize management of cholesterol on a case-by-case basis and encourage patient-provider discussions of risk before a decision on a treatment plan.

#
New cholesterol guidelines from the American Heart Association, American College of Cardiology and 10 other societies recommend a stepped approach including statins, ezetimibe and PCSK9 inhibitors in patients with prior CVD at very high risk for another event.
Source: Adobe Stock

“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 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 guidelines, 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, feature 10 important take-home messages:

  • A lifetime of heart-healthy lifestyle should be emphasized for all patients.
PAGE BREAK
  • 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 they cannot achieve an LDL target of < 70 mg/dL on statin therapy. 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%.
  • 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.
  • In patients aged 40 to 75 years with diabetes and LDL at least 70 mg/dL, moderate-intensity statin therapy should be started regardless of 10-year ASCVD risk.
  • For adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and 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 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 adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and 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 < 0.9 and lipoprotein(a) 50 mg/dL or higher.
  • For adults aged 40 to 75 years with LDL 70 mg/dL or higher, without diabetes and with 10-year ASCVD risk of 7.5% to 19.9%, if 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 atherosclerotic CVD.
PAGE BREAK

“A CAC score of 0 means the 10-year event rates are likely to be below the range where statins provide a net benefit,” Stone said at the press conference.

  • 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 guidelines have 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.”

Sidney C. Smith Jr.

The guidelines were simultaneously published in Circulation and the Journal of the American College of Cardiology. – by Erik Swain

References:

Grundy SM, et al. 2018 AHA/ACC Cholesterol Clinical Practice Guidelines. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

Grundy SM, et al. Circulation. 2018;doi:10.1161/CIR.0000000000000625.

Grundy SM, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.11.002.

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

    Perspective
    Mark A. Hlatky

    Mark A. Hlatky

    One of the most important developments of the new guidelines is the idea of personalizing recommendations. One size does not fit all. Doctors should have a conversation with their patients about initiating treatment if they are primary prevention.

    Another important aspect is that we are explicitly addressing the value of treatments. Most recommendations in our guidelines ignore the costs. But in some areas where guidance is needed, we tried to make evidence-guided value statements. This is important because it shows that we need to consider value when we make recommendations.

    We need to re-evaluate our value models now that price reductions have been made to the PCSK9 inhibitors to determine if there is any effect on cost-effectiveness and value.

    • Mark A. Hlatky, MD, FACC, FAHA
    • Professor of Health Research Policy
      Professor or Medicine
      Stanford Health Care

    Disclosures: Hlatky is a member of the writing committee for the guidelines. He reports no relevant financial disclosures.

    Perspective
    Mary Norine Walsh

    Mary Norine Walsh

    I was very pleased that shared decision-making was such an important part of this document. The decision regarding treatment of risk factors is exactly the scenario in which shared decision-making should be used, because it comes at a pivot point in a patient’s life where he or she is considering lifetime medications.

    The guideline mentions a number of other important options for cholesterol treatment that have become more prevalent since the previous guideline. CAC scoring is discussed as a helpful way of deciding on a treatment plan. At this time, most private insurers do not cover CAC screening, and it is expensive out of pocket, making many patients hesitant to do it. But inclusion in the guidelines may change that.

    The guidelines endorsing the benefit of ezetimibe and PCSK9 inhibitors may also influence coverage decisions, especially for insurers who will not cover PCSK9 inhibitors without a major pre-approval process.

    Another important piece of the guidelines is the inclusion of a risk enhancement factor calling attention to women with preeclampsia. That preeclampsia confers elevated CVD risk is not common knowledge among primary care physicians and cardiologists.

    • Mary Norine Walsh, MD, MACC
    • Cardiology Today Editorial Board Member
      St. Vincent Heart Center, Indianapolis
      Past President, American College of Cardiology

    Disclosures: Walsh reports no relevant financial disclosures.

    Perspective
    Roger S. Blumenthal

    Roger S. Blumenthal

    In terms of CAC scoring, these guidelines are very similar to those of the Society of Cardiovascular Computed Tomography in that for a broad intermediate-risk group, if the patient is unsure of how to proceed or the physician is not sure that the calculation truly reflects the risk, a coronary calcium score is a very reasonable way to proceed. For people who are inclined to go on statin therapy and do not have any misgivings about it, I’d much rather them go on it. But in reality, most people are reluctant to go on medicine for 10 years or more. This broad intermediate-risk group includes up to half the patients we see.

    A great section in the document discusses statin-related side effects. We will often have a washout period where a patient is not on a statin, and then give a low dose of a statin. For example, with rosuvastatin, cut a 5-mg tablet in half, have the patient try that twice per week for 1 month and see how well they tolerate it. Then, slowly try to increase the dose. If necessary, consider ezetimibe for its synergistic effects. There is helpful information in the statin-associated symptoms section.

    The document notes that about 80% of all CV events are preventable. We want to emphasize healthy lifestyle habits earlier to prevent diabetes, hypertension, dyslipidemia and other conditions. This document makes strong use of the idea about doing lifetime risk assessment in people between 20 and 59 years of age. That helps us understand who is at high risk or low risk long-term.

    The document addresses many of the critiques of the 2013 guidelines and I think it will be very well-received.

    • Roger S. Blumenthal, MD
    • Cardiology Today Prevention Section Editor
      Johns Hopkins Ciccarone Center for the Prevention of Heart Disease

    Disclosures: Blumenthal is a member of the writing committee for the guidelines. He reports no relevant financial disclosures.

    Perspective
    Steven E. Nissen

    Steven E. Nissen

    The 2013 guidelines received a lot of criticism. What is interesting about the new guidelines is that they 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
    • Cardiology Today Editorial Board Member
      Cleveland Clinic

    Disclosures: Nissen reports no relevant financial disclosures.

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