CHICAGO — The world of cholesterol management and coronary disease prevention has come a long way since 2013, when a major practice guideline document called for radical shifts in strategies for lowering low-density lipoprotein cholesterol (LDL-C), drawing praise, reproach, and puzzlement.
That document’s latest incarnation, unveiled here at the American Heart Association (AHA) Scientific Sessions 2018, preserves key ideas from the original and puts renewed focus on cherished principles that had been given a back seat in 2013.
Importantly, too, the AHA/American College of Cardiology (ACC) 2018 guideline on the management of blood cholesterol provides a concrete guidance on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, namely evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron).
The 2018 guideline retains one of the most controversial innovations of the 2013 document, a scoring system for 10-year atherosclerotic cardiovascular disease (ASCVD) risk, but has modified it to include more population-based data than before. But more fundamentally, it seems to slash the ASCVD risk calculator’s influence as a trigger for statin therapy.
Largely filling the influence gap are limited restoration of LDL-C treatment targets, especially in higher-risk groups, and a pervasive investment in doctor-patient communication for shared decision-making, especially for intermediate-risk primary prevention patients.
In the latter group, coronary artery calcium (CAC) scores are retained for limited use as a potential “tie-breaker” in the statin-or-not decision process.
The guideline recommends PCSK9 inhibitors, whose randomized trial underpinnings were established after 2013, primarily for patients with familial hypercholesterolemia (FH), and for patients at very high ASCVD risk with elevated LDL-C despite maximal statins and ezetimibe. In that latter group, initiation of nonstatin lipid-lowering therapy should be considered for anyone with an LDL-C that hasn’t fallen below 70 mg/dL.
“The numbers are back in the guidelines,” writing group member Roger S. Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland, told theheart.org | Medscape Cardiology. “The emphasis is on ‘lower is better’ with proven therapies.”
The AHA/ACC 2018 guideline on the management of blood cholesterol, endorsed by at least 10 other medical societies, is published today in the Journal of the American College of Cardiology and in Circulation to coincide with their grand unveiling at the AHA sessions.
The writing committee was chaired by Scott M. Grundy, MD, PhD, University of Texas Southwestern Medical Center at Dallas, and co-chaired by Neil J. Stone, MD, Northwestern University, Chicago, Illinois.
The new document carries over much from the 2013 guidelines, especially the four major categories of patients with different management needs for whom statins may be considered:
Primary prevention: that is, no clinical ASCVD or diabetes but LDL-C 70 mg/dL or higher and 7.5% or greater 10-year risk by the calculator;
No clinical ASCVD but with diabetes and LDL-C of 70 mg/dL or greater;
Secondary prevention: that is, clinical ASCVD without heart failure; and
Severe primary hypercholesterolemia (LDL-C ≥190 mg/dL), often called FH.
Primary Prevention: No Clinical ASCVD or Diabetes
Since the 2013 document, “We have revamped the approach to risk assessment in primary prevention, but it still starts with calculating a 10-year risk estimate,” writing committee member Donald Lloyd-Jones, MD, Northwestern University Feinberg School of Medicine, Chicago, said to theheart.org | Medscape Cardiology.
“That has to be starting point,” Lloyd-Jones said, because the risk score influences the intensity of the management program, whether by lifestyle modification or drug therapy.
“While the risk calculator has not been recalibrated, there’s much greater guidance now about how the patient and the clinician should approach the risk discussion that didn’t get as much attention in 2013,” Blumenthal said.
The 10-year risk score, he said, is in his view an “educated guess” that for most patients in the broad intermediate-risk range of 7.5% to less than 20% should be an opportunity for shared decision-making.
“That gray area, the intermediate range, now has much better emphasis in the guideline,” Blumenthal said. “An ASCVD risk score of, say, 10% or 15% does not automatically mandate a statin. But it should lead to a more detailed discussion. I think that’s a major step forward for these guidelines.”
To help in the shared decision-making process, the document specifies a number of “risk-enhancing factors” that are not considered in the risk calculator and, if present, “might push us to go ahead and prescribe a statin, if the patient is agreeable,” Lloyd-Jones said.
The risk enhancers include the following:
LDL-C of 160 mg/dL or greater, a C-reactive protein (high-sensitivity assay) of 2.0 mg/L or greater, apolipoprotein B of 130 mg/dL or greater, or elevated lipoprotein(a);
Ankle-brachial index less than 0.9;
Comorbid conditions, such as metabolic syndrome; chronic kidney disease (CKD); chronic inflammatory disorders, such as rheumatoid arthritis, lupus, or HIV; or premature menopause;
Family history of premature ASCVD;
Southern Asian ancestry; and
Elevated lifetime ASCVD risk.
The document says for patients at borderline ASCVD risk, that is a 10-year risk of 5% to less than 7.5%, the presence of risk enhancers would favor statin therapy with class IIb recommendation. The enhancers would favor statins with a class I recommendation for those at intermediate risk of 7.5% to less than 20%. For patients at high risk (ie, a score of 20% or higher), high-intensity statins are favored with a class 1 recommendation.
Importantly, “if after that discussion, the doctor and patient are still uncertain, or if the patient really wants a little bit more confirmation, we have designed specific recommendations about using coronary artery calcium screening,” Lloyd-Jones said. CAC imaging would be an option primarily for patients at intermediate risk.
If the CAC score is 0, “as it will be in about 50% of these people, then we say it’s reasonable to avoid a statin,” he said.
Patients with a CAC score of at least 100 Agatston units in the 75th percentile adjusted for age and sex “we say very clearly are a group that will benefit from statin therapy. Not only do we think they’re at higher risk, but indeed, their calcium scores indicate that they’ve got a significant burden of atherosclerosis.”
If the CAC score is in the indeterminate range of 1 to 99 Agatston units, the decision might be to initiate a statin or repeat the coronary calcium scan at least 2 years later. “And if it has changed rapidly, it would be an indicator that they might want to more strongly consider a statin,” Lloyd-Jones said.
Diabetes Without Clinical ASCVD
The document recommends that all patients with diabetes aged 40 to 75 years with an LDL-C of 70 mg/dL or higher be taking a moderate-intensity statin and do not need a calculated 10-year ASCVD risk assessment. A high-intensity statin, it states, should be considered for such patients with multiple risk factors.
The document affords some flexibility, however, even in patients with diabetes, Blumenthal said, “If the patient still is uncertain whether to go on lifelong statin therapy, as part of the risk discussion it is certainly reasonable for them to try a period of lifestyle changes that are more intensified, and then see if they get their A1c from the 7% range back down to the 6.5% or less range. Then also, with weight loss and exercise, maybe they’ll also improve their lipids.”
Secondary Prevention: Clinical ASCVD
For this group, the document recommends maximally tolerated statin therapy, and consideration of added ezetimibe for those do not reduce LDL-C by at least 50%, or to less than 70 mg/dL.
Lloyd-Jones said such patients are likely to see, on average, an additional 20% drop in LDL-C with the addition of ezetimibe. But then if LDL-C remains greater than 70 mg/dL, then “it’s reasonable to try a PCSK9 inhibitor in addition.”
Severe Primary Hypercholesterolemia, or FH
For patients in this category, who have an LDL-C greater than 190 mg/dL, “you don’t have to calculate their 10-year risk, we know they need treatment. So, maximally tolerated statin therapy for everybody,” Lloyd-Jones said.
If they do not then show a 50% reduction in LDL-C and it remains above 100 mg/dL, “then it’s reasonable to put them on ezetimibe first, and then consider PCSK9 inhibitors if the threshold is not yet achieved.”
The guidelines document advocates a “heart-healthy lifestyle across the life course” near the top as a kind of foundation for its more detailed sections on risk and medical regimens.
“Even if one gets started on a medication for cholesterol or blood pressure or both, the clinician should really emphasize ways to further improve their lifestyle over the next three months or six months,” Blumenthal said.
As the report notes, the ACC/AHA document was also approved by the American Association of Cardiovascular Pulmonary Rehabilitation, American Academy of Physician Assistants, Association of Black Cardiologists, American College of Preventive Medicine, American Diabetes Association, American Geriatrics Society, American Pharmacists Association, American Society for Preventive Cardiology, National Lipid Association, and Preventive Cardiovascular Nurses Association.
“There were 24 of us on the writing committee, and exactly zero of us had relevant relationships with industry or conflicts of interest,” Lloyd-Jones told theheart.org | Medscape Cardiology.