From the NLA President and Editors of LipidSpin: New Clinical Guidelines: Paving the Road Ahead

“Knowing is not enough; we must apply. Willing is not enough; we must do.” This remark by Goethe introduces readers to the rationale for the Institute of Medicine of the National Academies Committee on Standards for Developing Trustworthy Clinical Practice Guidelines: Guidelines We Can Trust 2011.

If you were asked to compose a set of guidelines to advise clinicians on the best approach to cholesterol management, how would you write them? What if that same set of guidelines was meant to inform health systems? Insurers? Other national health systems? They would have to be one-size-fits-all. The guidelines would have to be concise, clear, evidence-based, flexible, universal, simple. They would have to provide the best advice for the greatest number of patients without compromising advice to individuals. We think the 2018 Cholesterol Clinical Practice Guidelines (CPGs)(1) accomplished that, and we applaud the effort of the Writing Committee.

As you know, the American Heart Association (AHA) and American College of Cardiology (ACC) enlisted the assistance of 10 other stakeholder organizations, including the National Lipid Association (NLA), to ensure best practices, consensus and distribution of their recommendations making up the 2018 Guidelines on the Management of Blood Cholesterol, released at AHA Scientific Sessions in November 2018. Look for an upcoming LipidSpin issue dedicated exclusively to the Guidelines, where NLA member authors will weigh in on their merits (and shortcomings). Based upon the response to retention hypothesis of atherosclerosis, observational, genetic and clinical trial evidence, therapeutic lipid and lipoprotein management of ASCVD risk should emphasize the following:

• A healthy lifestyle is the foundation of care for all individuals.
• One should reduce apolipoprotein B (apoB) containing lipoprotein levels (primarily represented by the lowdensity lipoprotein cholesterol (LDLC)) as much as possible by enhancing peripheral clearance of therogenic lipoproteins, using statin drugs as the foundation of pharmacotherapy.
• The statin dose should be one used in randomized placebo controlled clinical trials (RPCTs), higher intensity preferred over moderate, and the goals for intensity of response should be matched to ASCVD risk.
• Since clinicians and patients do not always know their pre-treatment lipid levels, there should also be thresholds over which intensification of therapy should be considered.
• Since there is a high rate of attrition with statin therapy, regular monitoring to ensure medication tolerability, response to therapy and adherence to care is recommended. This begins with education and a shared discussion, and the relationship has to be maintained and reinforced over time.

Since national CPGs are written for general use by clinicians, health systems, governing bodies and insurers, simple, clear messaging with distinct recommendations are necessary. This approach will invariably leave debate at the margins where nuance and experience are critical, and we look forward to those discussions in LipidSpin and upcoming NLA meetings. This iteration of the Cholesterol Guidelines emphasizes the messaging, establishing the 10 “takeaway messages:”

1. In all individuals, emphasize a hearthealthy lifestyle across the life course.
2. In patients with clinical ASCVD, reduce LDL-C with high-intensity statin therapy or maximally tolerated statin therapy.
3. In very high-risk ASCVD, use LDL-C of 70 mg/dL to consider addition of nonstatins to statin therapy
4. In patients with severe hypercholesterolemia (LDL-C ≥190 mg/dL), begin high-intensity statin therapy without calculating 10-year ASCVD risk.
5. In patients 40-75 years with diabetes mellitus (DM) and LDL-C ≥70 mg/dL, start moderate-intensity statin therapy without calculating 10-year ASCVD risk.
6. In adults 40-75 years evaluated for primary ASCVD prevention, have a clinician–patient risk discussion before starting statin therapy
7. In adults 40-75 years without DM and with LDL-C ≥70 mg/dL, at a 10-year ASCVD risk of ≥7.5%, start a moderateintensity statin if a discussion of treatment options favors statin therapy
8. In adults 40-75 years without DM and 10-year risk of 7.5%-19.9% (intermediate risk), risk-enhancing factors favor initiation of statin therapy.
9. In adults 40-75 years without DM and with LDL-C ≥70-189 mg/dL, at a 10-year ASCVD risk of ≥7.5%-19.9%, if a decision about statin therapy is uncertain, consider measuring CAC.
10. Assess adherence and percentage response to LDL-C–lowering medications and lifestyle changes with repeat lipid measurement 4-12 weeks after statin initiation or dose adjustment, repeated every 3-12 months as needed.

The 2018 Guidelines outline the critical role of lifestyle intervention (message No. 1), and reminds linicians that treatment is not bestowed upon patients, but rather is an agreed-upon conclusion that takes into consideration the above concerns (message No. 6). They also reinforce the critical aspect of assessment of response and adherence to therapy (message No. 10), which informs outcomes and recommendations of care.

The remainder of the messages are specific, content-driven recommendations with a review of supporting evidence. The four main categories of risk are identified (clinical ASCVD, LDL-C >190 mg/dL, DM and primary prevention with moderate ASCVD risk). They introduced opportunity to integrate advanced-risk evaluation by acknowledging there is a range of ASCVD amongst patients in those risk categories and suggested evidence-based criteria for enhanced stratification. In particular, apolipoprotein B, lipoprotein (a) and coronary artery calcium scoring (CACS) are tools that lipidologists use regularly but have largely remained a “hidden secret.” Hopefully, the new Guidelines will lead to greater utilization of these important risk markers. They also reinforce the importance of treatment thresholds, giving clinicians (patients and payers) clear recommendations for when there is strong enough evidence to intensify pharmacotherapy.

Individual clinicians and patients can treat “beyond the Guidelines,” but should recognize they do so with less evidence supporting care. In fact, there are many examples where this makes sense, but it is not difficult to come up with a list of examples where this backfired (using extended release niacin in our patients achieving low LDL-C with moderate intensity statin? Alpha-blockers as monotherapy for hypertension? Lidocaine for ventricular ectopy during myocardial infarction?). As such, these approaches are not endorsed, and clinicians are cautioned to proceed with care when adding therapy for which the evidence is not based upon randomized placebo control trials (RPCTs).

We advise patience and support rigorous clinical scientific investigation going forward. Many clinical questions remain in our field, and while we have to apologize for our shortcomings to our patients when they jump to reasonable conclusions about potential benefit (e.g. PCSK9i for primary prevention instead of statins, niacin or PCSK9i for high Lp(a)), clinical care is about helping our patients make the best decisions in the present world, helping them access best available care, providing support and managing expectations.

For now, let’s thank our NLA representatives to the Guidelines writing team, Carl E. Orringer, MD, FNLA; Joseph J. Saseen, PharmD, FNLA; and Lynne T. Braun, PhD, CNP, CLS, FNLA, and our colleagues from all 12 organizations. We appreciate your hard work and excellence. In particular, we thank you for reminding us of the critical importance of the healthy lifestyle, the emphasis on communication with our patients and the need for longterm support for long-term therapy.

Disclosure statement: Dr. Brown has served as Consultant for Akcea, Amgen, Kowa, Regeneron and Sanofi. Dr. Soffer has served as Consultant for Amgen Inc, Akcea Therapeutics, Medicure, Regeneron, and has been a disease management Speaker on disease states (FCS and FH respectively) for Amgen Inc and Sanofi. Dr. Willard has received honoraria from Regeneron, Sanofi, Amgen and Akcea.