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.
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.
A Product Manager with expertise in pharma marketing and sales operations