New Cholesterol Treatment Guidelines: A Mass General Perspective

At the 2018 American Heart Association (AHA) Scientific Sessions, the American College of Cardiology (ACC) and the AHA released new cholesterol guidelines. These new guidelines represent the first major update since 2013. Pradeep Natarajan, MD, MMSc, director of Mass General's Preventive Cardiology Program, explains the significance of this update, and how these changes will impact the way he treats patients.

Q: What were the determining factors in updating the cholesterol guidelines?

Natarajan: Atherosclerotic cardiovascular disease (ASCVD) remains one of the principal causes of morbidity and premature mortality worldwide. A key focus of cardiovascular medicine is prevention of the onset of ASCVD as well as recurrent events. One of the central strategies for prevention is the lowering of plasma cholesterol, which is why the cholesterol guidelines saw an update in 2018.

The most recent cholesterol guidelines were released in 2013, and since then, non-statin medicines like ezetimibe and PCSK9 monoclonal antibodies have been shown to reduce recurrent cardiovascular disease risk. As such, these recommendations are now incorporated in the 2018 guidelines.

In recognition of the additional costs to the health care system—as well as to patients—the guidelines also now subset individuals with ASCVD into a new group with "very high risk" ASCVD. These individuals have had recurrent major ASCVD events despite guideline-appropriate therapies or a prior major ASCVD event, along with multiple risk factors. In addition to attaining LDL cholesterol-lowering >50%, we now also target LDL cholesterol < 70 mg/dl for these individuals with statins, ezetimibe and PCSK9 inhibitors as needed.

Another challenge with the 2013 guidelines was the identification of suitable statin candidates, without severe hypercholesterolemia or diabetes mellitus, to prevent a first ASCVD event. Previously, such individuals were identified on the basis of a 10-year ASCVD estimated risk of >7.5% (previously termed "high risk"), but it was recognized that this represented a highly heterogeneous group with respect to preferences and statin suitability. However, in the update guidelines, "high risk" is >20% 10-year risk and 7.5-19.9% is termed "intermediate risk."

For those with 7.5-19.9% 10-year risk, there is now more emphasis on shared decision-making between patients and providers to determine statin suitability. This includes the incorporation of "risk enhancing" factors like family history, apolipoprotein B, lipoprotein(a) and others that were previously described in 2013. It also means new factors, such as South Asian ancestry, history of pre-eclampsia, history of premature menopause and a chronic inflammatory illness. Additionally, if equipoise remains, cardiac computerized tomography (CT) to quantify coronary artery calcification may help adjudicate. The use of cardiac CT to downgrade risk at this estimated risk level is new to the 2018 guidelines.

Q: How much will the new cholesterol guidelines change your approach to patient care?

Natarajan: These guidelines now provide more concrete granularity about when to consider PCSK9 inhibitors. My hope is that this will improve access to our patients who would benefit from more aggressive LDL cholesterol-lowering. The FDA label for these medicines currently does not provide such clarity. By returning to specific treatment targets, prescribers like me are now able to directly point to the 2018 guidelines when advocating for prescription approvals.

When prescribing preventive medicines to prevent the onset of cardiovascular disease, discussions involve:

• Estimating and communicating risk
• Strategies to refine risk where appropriate
• Therapies to mitigate risk
• Downsides of therapies to mitigate risk

Now, the new guidelines provide the new tools to aid this discussion through the incorporation of various "risk-enhancing" factors that have each been independently associated with cardiovascular disease risk.

I have always considered cardiac CT for the quantification of coronary artery calcification important in helping adjudicate statin suitability. There are still several outstanding questions about the appropriate use of cardiac CT for coronary artery calcification scoring that have not been assessed in prospective clinical trials to-date. Thus, the use of coronary artery calcification scoring also requires a conversation about:

• Cost
• Modest risk of radiation
• Risk of incidental findings and downstream tests/procedures
• Anticipated management changes
• The uncertainties of coronary artery calcification-driven management changes

The stronger incorporation of coronary artery calcification scoring into the 2018 guidelines will likely lead to increased use, including in my practice.

Q: How would you advise fellow clinicians to adapt these new guidelines into their practice?

Natarajan: Fortunately for practicing clinicians, most of the guidelines remain the same and the risk estimator for primary prevention also remains the same. The first two pages of the guideline document are high-yield with the top takeaways of the guidelines. At minimum, all primary care doctors and cardiovascular specialists should read these two pages.

Additionally, the AHA will soon release a series of podcasts to help disseminate key points and nuances of the 2018 guidelines. I am delighted to be one of the organizers and participants of this series.

Q: Based on these new guidelines, what are indicators that might lead primary care physicians to consider referring patients to a specialized cardiologist or center?

Natarajan: Effective cardiovascular disease prevention involves both the incorporation of guidelines into practice and educating patients about cardiovascular disease prevention. For many patients, the inherent uncertainties of risk estimation can lead to a large spectrum of cardiovascular health notions. Distillation of this information in the press is typically not personalized, which often leads to important questions.

A key concept for primary prevention is increased flexibility for shared decision-making between patients and providers. This may actually lead to more complexity than a standard primary care appointment can allow. If additional questions persist—related to statin suitability, risk refinement, etc.—referral to preventive cardiology can be helpful.

A key challenge is the estimation of risk in young individuals (< 50 years). For these individuals, particularly if there are clinical risk factors present, such as a family history of premature ASCVD, a referral to a preventive cardiologist can be helpful. We can work to develop a plan for risk estimation and mitigation, as well as offer clinical surveillance.

Additionally, there is likely to be expanded use—or at least increased recognition—of cardiac CT for coronary artery calcification scoring. If there is equipoise, referral to preventive cardiology can help guide both its use and interpretation.

Q: Do you think these new guidelines will result in greater emphasis on research into cholesterol?

Natarajan: The periodic revision of these guidelines and others highlight that cardiovascular medicine is dynamic. We continue to incorporate new information to improve the health of our patients. Looking forward, there are important questions that persist requiring additional research, particularly around the identification of high-risk young individuals, LDL cholesterol targets, lowering of triglyceride-rich lipoproteins, use of "risk enhancing" factors and the incorporation of cardiac CT in statin decisions.

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