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. Author manuscript; available in PMC: 2022 Apr 1.
Published in final edited form as: Curr Opin Endocrinol Diabetes Obes. 2021 Apr 1;28(2):114–121. doi: 10.1097/MED.0000000000000608

Transatlantic Guidelines on Dyslipidemia and Cardiovascular Risk: Key Differences across the Pond

Ali M Agha 1, Salim S Virani 1,2, Christie M Ballantyne 1
PMCID: PMC7963270  NIHMSID: NIHMS1678032  PMID: 33395089

Abstract

Purpose of review:

The purpose of this review is to compare and contrast the key messages from the 2018 American Heart Association (AHA)/American College of Cardiology (ACC) Multisociety Guideline on the Management of Blood Cholesterol and the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) Guidelines for the Management of Dyslipidemias. We also review some of the evidence that served as the basis for these guidelines and share our opinion regarding these guidelines.

Recent findings:

Patients with atherosclerotic cardiovascular disease (ASCVD), severe hypercholesterolemia, familial hypercholesterolemia, or diabetes should be treated aggressively with lipid-lowering therapy. In addition to traditional risk factors included in risk scores, assessment of risk enhancers/modifiers may improve risk stratification. The addition of ezetimibe ± proprotein convertase subtilisin/kexin type 9 inhibitors plays an integral role in the management of very-high-risk ASCVD patients; the ESC/EAS guidelines support more aggressive use of these medications.

Summary:

Both the AHA/ACC Multisociety and ESC/EAS guidelines provide an evidence-based approach to management of blood cholesterol. The greatest difference between these two guidelines is the classification and recommended management of very-high-risk patients. Implementation of either guideline will likely lead to improved ASCVD outcomes compared with current treatment practice.

Keywords: Hyperlipidemia, Cholesterol, Risk stratification, Atherosclerotic cardiovascular disease

Introduction

The most recent American Heart Association (AHA)/American College of Cardiology (ACC) Multisociety Guideline on the Management of Blood Cholesterol was published in November 2018 [1] and greatly expanded on the 2013 recommendations [2]. Just nine months later, the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) Guidelines for the Management of Dyslipidemias [3] were published. Both guidelines provide classes of recommendations (where class I is a strong recommendation) and the levels of evidence used to support these recommendations (where level A is strong evidence from randomized controlled trials or meta-analyses). The basic principles of both guidelines have much in common, but there are some key differences, especially regarding the classification of very-high-risk patients (Tables 1a and 1b) and how aggressively to manage dyslipidemia in these individuals. The AHA/ACC Multisociety guidelines used only randomized controlled trial data to inform treatment recommendations for these patients, whereas the ESC/EAS guidelines extrapolate from data demonstrating that absolute risk reduction for an atherosclerotic cardiovascular disease (ASCVD) event is greatest in those with highest baseline risk [4]. These differences may require clinicians to analyze these guidelines critically and make their own decisions on how best to manage patients with multiple risk factors for ASCVD.

Table 1a.

2018 AHA/ACC Multisociety Blood Cholesterol Guidelines: Risk Stratification [1]

Very-High-Risk

  • History of multiple major ASCVD events*

  • 1 major ASCVD event* and multiple high-risk conditions†

High-Risk

  • ASCVD (unless very-high-risk as defined above)

  • Age 40–75 years without clinical ASCVD or diabetes mellitus and with LDL-C 70–189 mg/dL and 10-year ASCVD risk ≥20% by pooled cohort equation estimate

Intermediate-Risk

  • Age 40–75 years without clinical ASCVD or diabetes mellitus and with LDL-C 70–189 mg/dL and 10-year ASCVD risk ≥7.5% to <20% by pooled cohort equation estimate

Borderline-Risk

  • Age 40–75 years without clinical ASCVD or diabetes mellitus and with LDL-C 70–189 mg/dL and 10-year ASCVD risk ≥5% to <7.5% by pooled cohort equation estimate

Low-Risk

  • Age 40–75 years without clinical ASCVD or diabetes mellitus and with LDL-C 70–189 mg/dL and 10-year ASCVD risk <5% by pooled cohort equation estimate
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*

ASCVD events: acute coronary syndrome within past 12 months; history of myocardial infarction (other than recent acute coronary syndrome event), history of ischemic stroke, symptomatic peripheral arterial disease (claudication with ankle–brachial index <0.85, previous revascularization, or previous amputation).

†

High-risk conditions: age ≥65 years, heterozygous familial hypercholesterolemia, prior coronary artery bypass graft or percutaneous coronary intervention not occurring in the setting of one of the aforementioned ASCVD events, diabetes mellitus, hypertension, chronic kidney disease (estimated glomerular filtration rate 15–59 mL/min/1.73 m2), current smoking, persistent LDL-C ≥100 mg/dL despite maximally tolerated statin and ezetimibe, congestive heart failure.

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol.

Table 1b.

2019 ESC/EAS Blood Cholesterol Guidelines: Risk Stratification [3]

Very-high-risk (LDL-C goal <55 mg/dL)

  1. Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD includes previous acute coronary syndrome (myocardial infarction or unstable angina), stable angina, coronary revascularization (percutaneous coronary intervention, coronary artery bypass grafting, and other arterial revascularization procedures), stroke and transient ischemic attack, and peripheral arterial disease. Unequivocally documented ASCVD on imaging includes findings known to be predictive of clinical events, such as significant plaque on coronary angiography or computed tomography scan (multivessel coronary disease with two major epicardial arteries having >50% stenosis), or on carotid ultrasound

  2. Diabetes with target organ damage, or ≥3 major risk factors, or early-onset type 1 diabetes of long duration (>20 years)

  3. Severe chronic kidney disease (eGFR < 30 mL/min/1.73m2)

  4. A calculated SCORE of ≥10% for 10-year risk of fatal cardiovascular disease

  5. FH with ASCVD or with another major risk factor

High-risk (LDL-C goal <70 mg/dL)

  1. Markedly elevated single risk factors, in particular total cholesterol >8 mmol/L (>310 mg/dL), LDL-C >4.9 mmol/L (>190 mg/dL), or blood pressure ≥180/110 mmHg

  2. FH without other major risk factors

  3. Diabetes without target organ damage, with diabetes duration ≥10 years or another additional risk factor

  4. Moderate chronic kidney disease (eGFR 30–59 mL/min/1.732)

  5. SCORE ≥5% and <10% for 10-year risk of fatal cardiovascular disease

Moderate-risk (LDL-C goal <100 mg/dL)

  1. Type 1 diabetes and age <35 years, or type 2 diabetes and age <50 years, with diabetes duration <10 years and without other risk factors.

  2. SCORE ≥1% and <5% for 10-year risk of fatal cardiovascular disease

Low-risk (LDL-C goal <116mg/dL)

  1. SCORE <1% for 10-year risk of fatal cardiovascular disease
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Abbreviations: ASCVD, atherosclerotic cardiovascular disease; eGFR, estimated glomerular filtration rate; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; SCORE, Systematic Coronary Risk Estimation.

In this review, we discuss the similarities between these guidelines and highlight key differences. We also review some of the evidence that served as the basis for these guidelines and share our opinion regarding these recommendations.

Similarity: Lifestyle Interventions

Both the AHA/ACC Multisociety and ESC/EAS guidelines emphasize the importance of a heart-healthy diet, recommending foods that are components of the Dietary Approaches to Stop Hypertension (DASH) diet (which has been shown to reduce blood pressure [5]) as well as the Mediterranean diet (which has been shown to reduce the incidence of primary major adverse cardiac events in high-risk individuals [6]). Both guidelines also recommend frequent physical activity for all patients and weight loss for overweight/obese patients (especially those with features consistent with metabolic syndrome). In addition to medical management, patients should be counseled on the importance of lifestyle interventions at every outpatient visit.

Similarity: Medical Management to Reduce Low-Density Lipoprotein Cholesterol

The target of therapy in both the AHA/ACC Multisociety and ESC/EAS guidelines is the use of statin therapy to reduce the levels of atherogenic lipoprotein in the blood, which is primarily low-density lipoprotein (LDL) [7]. Clinicians measure LDL cholesterol (LDL-C), and therefore, reductions in LDL-C are the target of therapy in both sets of guidelines. The Cholesterol Treatment Trialists performed a meta-analysis including more than 39,000 patients with median follow-up of ≥5 years that demonstrated that for each 1-mmol/L (38.7-mg/dL) reduction in LDL-C, there was a stepwise reduction in the incidence of myocardial infarction, ischemic stroke, and revascularization [8]. These findings support the mantra “less is more” for LDL-C. Furthermore, the absolute risk reduction for major cardiovascular events and mortality with LDL-C reduction was proportional to the absolute baseline risk, suggesting that individuals at greatest risk for ASCVD events have the most to gain from reducing LDL-C. Both the AHA/ACC Multisociety and ESC/EAS guidelines recommend assessment of LDL-C levels at baseline and repeat measurements of LDL-C after initiation of lipid-lowering therapy (LLT) to monitor response and determine adherence [9, 10*].

Similarity: Management of High-Risk Groups

Both guidelines recommend initiation of LLT without calculating a risk score in patients with LDL-C ≥190 mg/dL. In these individuals, AHA/ACC Multisociety guidelines recommend initiation of high-intensity statin therapy; if LDL-C remains ≥100 mg/dL, the addition of ezetimibe ± proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) in a stepwise fashion can be considered. The ESC/EAS guidelines recommend strongly considering the diagnosis of familial hypercholesterolemia (FH) in individuals with LDL-C ≥190 mg/dL, and suggest treating those with FH and ASCVD or another major risk factor as very high risk, whereas those with FH and no ASCVD or major risk factors are classified as high risk (Table 1b). Patients with FH have a high risk of developing ASCVD compared with the general population even if they are prescribed LLT, which suggests they should be treated more aggressively [11].

ASCVD remains a major cause of morbidity and mortality in diabetic patients, especially compared with the general population [12]. Consequently, LLT may be initiated in diabetic patients without calculating a risk score. In adults with diabetes aged 40–75 years, the AHA/ACC Multisociety guidelines recommend using at least moderate-intensity statin therapy, and considering high-intensity statin therapy to achieve an LDL-C reduction of ≥50% from baseline, in patients with diabetes with multiple other ASCVD risk factors (diabetes-specific risk enhancers). Likewise, the ESC/EAS guidelines recommend treating nearly all diabetic patients (with the exception of those who are relatively young, recently diagnosed, and with no other ASCVD risk factors) as either high risk or very high risk (see Table 1b).

Similarity: Management of Hyperlipidemia in the Elderly

In individuals aged ≥75 years, both guidelines state that it is reasonable to consider continuation or initiation of statin therapy.

Similarity: Risk Stratification

Although some of the aforementioned patients meet clinical criteria that mandate the initiation of statin therapy, many primary-prevention patients require the calculation of a risk score to determine the need for statin therapy. The AHA/ACC Multisociety guidelines recommend using pooled cohort risk equations to determine the likelihood of an initial ASCVD event within the next 10 years, whereas the European Systematic Coronary Risk Estimation (SCORE) system provides the likelihood of death due to cardiovascular disease. The SCORE can be multiplied by approximately 3 to estimate the risk of an ASCVD event (the multiplier is higher in women and lower in the elderly), and it is recalibrated for high-risk versus low-risk regions of Europe. The components of both risk scores are extremely similar.

Both of these risk calculators have limitations. ASCVD risk may be overestimated in the elderly [13]. Additionally, these risk calculators may underestimate the influence of atypical risk factors for ASCVD such as inflammatory conditions [14, 15], exposure to mediastinal radiation [16], and South Asian ancestry [17, 18*]. Of note, the ASCVD risk calculator derived from the pooled cohort equations in the AHA/ACC Multisociety guidelines is race and sex specific, based on 4 different pooled cohort equations (1 each for Caucasian men and women and African American men and women). The AHA/ACC Multisociety guidelines also include a separate section on race and ethnicity. Although the SCORE accounts for low-risk vs high-risk regions of Europe, race is not incorporated, and the ESC/EAS guidelines have no specific recommendations based on race or ethnicity.

Difference: Interpretation of Risk Score

The AHA/ACC Multisociety guidelines recommend initiation of moderate-intensity statin therapy in individuals without known ASCVD aged 40–75 years who have ASCVD risk ≥7.5% but <20% (intermediate risk) and LDL-C ≥70 mg/dL, with the aim of reducing LDL-C by ≥30%. Initiation of therapy should follow a patient-centered discussion on ASCVD risk factor modification as well as the pros and cons of statin therapy. Presence of ASCVD risk enhancers (discussed below) also supports initiation of statin therapy in intermediate-risk patients. Of note, assessment of coronary artery calcium (CAC) on computed tomography in intermediate-risk patients (excluding those with diabetes, current cigarette smoking, or a family history of premature ASCVD) may further aid the decision of whether to initiate statin therapy, as it was shown to improve risk stratification in one meta-analysis [19] and has proven to be cost-effective [20]. Among these individuals, statin therapy may be delayed or withheld in the absence of CAC, whereas a CAC score of ≥100 favors initiation of statin therapy. Additionally, high-intensity statin therapy is recommended in individuals with ASCVD risk ≥20%, with the aim of reducing LDL-C by ≥50%. In contrast, the ESC/EAS guidelines recommend achievement of a specific LDL-C goal based on the SCORE (Table 1b), but also acknowledge that CAC assessment may be used to guide statin therapy. A CAC score >100 may reclassify patients to a higher-risk category.

Difference: Risk Enhancers versus Risk Modifiers

In the AHA/ACC Multisociety guidelines, risk enhancers are patient attributes that may favor initiation of statin therapy among intermediate-risk patients and may help account for some risk factors not included in the pooled cohort equation. Risk-enhancing factors include family history of premature ASCVD, LDL-C levels ≥160 mg/dL (≥4.1 mmol/L), metabolic syndrome, chronic kidney disease, chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, or human immunodeficiency virus/acquired immunodeficiency syndrome), history of preeclampsia or premature menopause, high-risk race/ethnicities (e.g., South Asian), ankle–brachial index <0.9, apolipoprotein B levels ≥130 mg/dL, lipoprotein(a) levels >50 mg/dL or >125 nmol/L, and persistent elevations of triglycerides ≥175 mg/dL.

Similarly, the ESC/EAS guidelines describe risk modifiers to be considered in risk assessment but include additional factors also associated with increased ASCVD risk, such as social deprivation/lower socioeconomic status [21], physical inactivity, obstructive sleep apnea, left ventricular hypertrophy, and atrial fibrillation. Interestingly, the ESC/EAS guidelines include the presence of carotid plaque (which has been shown to improve risk stratification [22, 23]) as a risk modifier, but the AHA/ACC Multisociety guidelines do not. However, the ESC/EAS guidelines acknowledge that CAC assessment outperforms measurement of carotid intima–media thickness for improving risk stratification, and neither guideline establishes a role for carotid intima–media thickness in risk assessment [24].

Both the AHA/ACC Multisociety and ESC/EAS guidelines support the use of apolipoprotein B and lipoprotein(a) to help stratify risk; apolipoprotein B–containing lipoproteins are directly involved in the development of ASCVD [7], and lipoprotein(a) has been shown to have a causal association with risk for myocardial infarction [25]. However, the ESC/EAS guidelines more strongly support the use of these biomarkers, recommending measurement of lipoprotein(a) once in everyone and providing specific treatment goals for apolipoprotein B (<65 mg/dL, <80 mg/dL, and <100 mg/dL in patients with very high, high, and moderate ASCVD risk, respectively).

Difference: Definition and Management of Very-High-Risk Patients

For patients with documented ASCVD, both the AHA/ACC Multisociety and ESC/EAS guidelines recommend high-intensity or maximally tolerated statins as first-line therapy, intended to reduce LDL-C by ≥50%. However, the AHA/ACC Multisociety guidelines include in this category only patients with clinical ASCVD (acute coronary syndrome, history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral artery disease, including aortic aneurysm), whereas the ESC/EAS guidelines also include patients with ASCVD evidenced by imaging (significant plaque on coronary angiography, computed tomography, or carotid ultrasound) in the very-high-risk category.

Overall, the very-high-risk category is broader in the ESC/EAS guidelines and includes primary-prevention patients in addition to patients with established ASCVD, which leads to differences in recommended medical management. Tables 1a and 1b describe the risk categories in the AHA/ACC Multisociety and ESC/EAS guidelines. In very-high-risk patients, the AHA/ACC Multisociety guidelines recommend an LDL-C threshold of 70 mg/dL for considering the addition of ezetimibe ± PCSK9i in a stepwise fashion. In contrast, the ESC/EAS guidelines recommend an LDL-C goal of <55 mg/dL in very-high-risk patients, with consideration of an even lower LDL-C goal of <40 mg/dL if a patient has a second ASCVD event within 2 years of an index event, to be achieved through stepwise use of ezetimibe ± PCSK9i.

The support for these thresholds/goals and the use of ezetimibe ± PCSK9i to achieve desirable LDL-C is based on randomized controlled trials published between 2013 and 2018 which demonstrated an incremental benefit of adding these medications to statin therapy in patients with established ASCVD, including after an acute coronary syndrome. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated that use of ezetimibe in addition to simvastatin led to a greater reduction of LDL-C and improved cardiovascular outcomes after acute coronary syndrome compared with simvastatin alone [26]. The ODYSSEY Outcomes trial demonstrated that the PCSK9i alirocumab led to improved cardiovascular outcomes in patients with previous acute coronary syndrome already on maximally tolerated statin therapy [27]. Additionally, the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial demonstrated that addition of the PCSK9i evolocumab to statin therapy in patients with stable ASCVD led to greater LDL-C reduction and lower cardiovascular event rate compared with statin alone [28]. PCSK9i may also play an important role in patients who are statin intolerant, a condition affecting up to 20% of ASCVD patients [29]. The ODYSSEY Alternative [30] and Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects (GAUSS-2) [31] trials demonstrated that alirocumab and evolocumab, respectively, produced greater LDL-C reductions than ezetimibe in statin-intolerant patients.

FOURIER [32] and ODYSSEY Outcomes [33] both enrolled patients with an LDL-C level ≥70 mg/dL, which influenced the decision to set a threshold of 70 mg/dL for addition of PCSK9i to maximally tolerated statin and ezetimibe in the AHA/ACC Multisociety guidelines. However, the median LDL-C in the treatment arm of FOURIER was 30 mg/dL at 48 weeks after randomization, and the mean LDL-C in the treatment arm of ODYSSEY Outcomes was 40 mg/dL and 48 mg/dL at 4 and 12 months after randomization, respectively, which may have influenced the low LDL-C goals in the ESC/EAS guidelines. Furthermore, the ESC/EAS guidelines cite the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) as evidence that LDL-C <50 mg/dL was not associated with adverse outcomes including myalgia, muscle weakness, neuropsychiatric conditions, cancer, and diabetes mellitus [34].

Not only do the ESC/EAS guidelines have a broader definition of very-high-risk patients and a low LDL-C goal (compared with the AHA/ACC Multisociety threshold) for these individuals, but they also more broadly support the use of nonstatin LLT such as PCSK9i. The 2018 AHA/ACC Multisociety guidelines include a value statement for the use of PCSK9i; the very-high-risk category was based on data that suggest which clinical characteristics can identify patients with the highest event rates who may benefit the most (in absolute risk reduction) from PCSK9i [35]. A post hoc analysis from ODYSSEY Outcomes demonstrated that the absolute risk reduction for major adverse cardiac events with alirocumab was numerically greater in patients classified as very high risk according to the AHA/ACC Multisociety guidelines versus those who were not classified as such (2.1% versus 0.8%) [36], suggesting that the US guideline identifies patients who may derive a larger benefit of treatment with alirocumab. Furthermore, analysis of the Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies (SWEDEHEART) register, including more than 25,000 individuals who had a myocardial infarction, suggested that more than half of these individuals would be eligible for a PCSK9i (according to the ESC/EAS guidelines) after simulating the effect of maximal statin therapy and ezetimibe [37*]. These findings raise major concerns about the potential cost of routinely implementing the ESC/EAS guidelines especially in healthcare systems which may have limited resources [38].

Difference: Icosapent Ethyl

The results of the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) were published after the AHA/ACC Multisociety guidelines but before the ESC/EAS guidelines. REDUCE-IT demonstrated that in patients with ASCVD or with diabetes and multiple ASCVD risk factors who have elevated triglycerides despite statin therapy, the risk for ischemic events was significantly lower in those who received 2 grams of icosapent ethyl twice daily compared with those who received placebo [39]. The ESC/EAS guidelines, but not the AHA/ACC Multisociety guidelines, recommend use of this medication in patients considered very high risk or high risk who have elevated triglycerides (135–499 mg/dL) despite statin treatment, which may also include some patients who would not meet the inclusion criteria of REDUCE-IT.

Conclusion

Both the AHA/ACC Multisociety and ESC/EAS guidelines provide evidence-based recommendations for the management of blood cholesterol, with the intention of reducing the burden of ASCVD. The greatest difference between these guidelines is the classification and recommendations for management of very high risk patients. Tables 2a and 2b summarize the key similarities and differences between these two guidelines.

Table 2a.

Key Similarities between 2018 AHA/ACC Multisociety [1] and 2019 ESC/EAS [3] Guidelines

Key Similarities Recommendation
Medical management The primary goal of medical management is LDL-C reduction with LLT
Management of patients with LDL-C ≥190 mg/dL or diabetes Aggressive LLT in very-high-risk and high-risk groups, without calculation of risk score
Management of elderly patients (aged ≥75 years) Reasonable to continue or initiate LLT among elderly
Risk stratification Use of risk estimator (pooled cohort risk equations or SCORE) to estimate ASCVD risk
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Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; SCORE, Systematic Coronary Risk Estimation.

Table 2b.

Key Differences between 2018 AHA/ACC Multisociety [1] and 2019 ESC/EAS [3] Guidelines

Key Differences AHA/ACC Multisociety Recommendation ESC/EAS Recommendation
Risk adjustment “Risk enhancers” “Risk modifiers” (which are broader than “Risk enhancers”)
Lipoprotein(a) Can be used as a risk enhancer if measured Should be measured once during a lifetime as a “risk modifier”
Apolipoprotein B Can be used as a risk enhancer if measured Specific targets for apolipoprotein B (<65 mg/dL, <80 mg/dL, and <100 mg/dL in very-high-risk, high-risk, and moderate-risk patients)
Classification of very-high-risk patients Multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions (see Table 1a) Broader (see Table 1b)
Management of very-high-risk patients LDL-C threshold of 70 mg/dL to consider the addition of ezetimibe ± PCSK9i in a stepwise fashion LDL-C goal of <55 mg/dL (<40 mg/dL if a patient has second ASCVD event within 2 years of an index event)
Icosapent ethyl treatment No recommendation Use in very-high-risk or high-risk patients with elevated triglycerides (135–499 mg/dL) despite statin treatment
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Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor.

There is a large gap between guideline recommendations and actual clinical practice in both the United States and Europe [40*, 41]. This large gap supports the need for further investigation of implementation science methods that address: 1) the most effective approaches to disseminate these recommendations to providers; 2) the best strategies for successful implementation of these guidelines into different clinical settings; 3) the effectiveness of implementing these recommendations with respect to changing clinical outcomes [42].

Regardless of which of the two guidelines is implemented, either will likely lead to an improvement in cardiovascular outcomes compared with current practice. Effective implementation of either guideline may lead to an improvement in care and, consequently, cardiovascular outcomes in both primary and secondary prevention. Most importantly, the implementation of these guidelines should be tailored to the unique characteristics and treatment preferences of each patient. Clinicians should use these recommendations as a framework for central principles, but should also use clinical judgment to treat individual patients.

Key Points.

  • Patients with ASCVD, severe hypercholesterolemia, familial hypercholesterolemia, or diabetes should be treated aggressively with LLT.

  • In addition to traditional risk factors included in risk scores, risk enhancers/modifiers may improve risk stratification.

  • The addition of ezetimibe ± PCSK9i plays an integral role in the management of very-high-risk patients, and the ESC/EAS guidelines support more aggressive use of these medications.

Acknowledgements

Financial support and sponsorship: Salim S. Virani receives research support from the US Department of Veterans Affairs, World Heart Federation, and Tahir and Jooma Family. Christie M. Ballantyne was supported by National Institutes of Health grant R01-HL134320.

Footnotes

Conflicts of interest: Ali M. Agha has none to disclose. Salim S. Virani has received an honorarium from the American College of Cardiology (as associate editor for Innovations acc.org), and is a Steering Committee member for the PALM registry at Duke Clinical Research Institute (no financial remuneration). Christie M. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, and Roche Diagnostic, and is a consultant for Abbott Diagnostics, Akcea, Althera, Amarin, Amgen, Arrowhead, Astra Zeneca, Corvidia, Denka Seiken, Esperion, Gilead, Janssen, Matinas BioPharma Inc, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo.

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