Comparing Primary Prevention Recommendations

A Focused Look at United States and European Guidelines on Dyslipidemia

Neil J. Stone, MD; Roger S. Blumenthal, MD; Donald Lloyd-Jones, MD, ScM; Scott M. Grundy, MD, PhD

Disclosures

Circulation. 2020;141(14):1117-1120. 

In This Article

Abstract and Introduction

Introduction

This brief review of recent United States and European guideline recommendations for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) through the management of dyslipidemia/cholesterol compares the evaluation and treatment set forth in both guidelines (see the Table). The US 2018 American Heart Association/American College of Cardiology Multisociety Guideline (AHA/ACC)[1] emphasizes lifestyle in ASCVD prevention throughout the life course and expands the role of the clinician-patient risk discussion in decisions on statin initiation in those at borderline or intermediate risk. It recommends statin therapy for those with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dl or adults 40 to 75 years of age with diabetes mellitus. For lower risk primary prevention, it endorses a 3-pronged approach to facilitate shared decision making. It begins with calculating 10-year ASCVD risk and then personalizing risk assessment with risk enhancing factors and, if needed to resolve uncertainty, a coronary artery calcium score. The 10-year ASCVD risk score uses the validated Pooled Cohort Equations.[2]

The European 2019 European Society of Cardiology–European Atherosclerosis Society Dyslipidemia Guideline (ESC/EAS) endorses a 3 stage risk stratification process of clinical evaluation using cardiovascular disease (CVD) risk estimation with the SCORE system (European Systematic Coronary Risk Evaluation).[3] For primary prevention, ESC/EAS begins with clinical evaluation designed to identify high- and very high-risk conditions, including diabetes mellitus with estimation of target organ damage, other major risk factors and diabetes mellitus duration, moderate to severe chronic kidney disease, very high levels of individual risk factors, familial hypercholesterolemia, or a high-risk SCORE for fatal CVD.

The second stage uses the 10-year SCORE risk estimate recommended for asymptomatic individuals >40 years of age without CVD or the high-risk conditions mentioned earlier. The SCORE CVD risk estimate uses large representative database sets from Europe to predict CVD death as contrasted with the Pooled Cohort Equation's use of US data to predict both nonfatal and fatal ASCVD events. Both guidelines acknowledge the usefulness (in the populations in which they have been derived and validated) and limitations of risk scores.[2,3]

The third stage is the assessment of risk modifiers. ESC/EAS risk modifiers are more extensive than AHA/CC risk enhancers (see Table). The ESC/EAS recommend, in selected individuals, measuring factors such as apolipoprotein B, lipoprotein(a) (LpA) or high-sensitivity C-reactive protein, assessing family history of premature ASCVD, or using the presence of moderate atherosclerotic plaque on imaging to improve risk stratification and inform treatment decisions.

Thus, in the approaches to primary prevention, there are strong similarities. Both guidelines acknowledge the importance of apolipoprotein B-containing lipoproteins in atherosclerosis and endorse aggressive lowering of LDL-C in those at highest risk. Both underscore a heart-healthy lifestyle and use evidence from randomized controlled trials. Both recommend statins as initial therapy for those at elevated ASCVD risk. Also, both recommend randomized controlled trial–proven non-statins (ezetimibe or PCSK9 inhibitors) in specific individuals at higher risk. The latter include patients with severe hypercholesterolemia, including familial hypercholesterolemia who merit treatment early in life.

Both guidelines require follow-up testing of LDL-C to determine treatment adequacy and assess percent LDL-C lowering. The ESC/EAS is more aggressive with non-statins by recommending their use when patients fail to reach specific targets for LDL-C; more subsequent testing and pharmacologic treatment will likely be needed to get individuals below arbitrary LDL-C goal levels. AHA/ACC focuses on net benefit that considers cost-effectiveness studies. In ESC/EAS, even low-risk individuals have a goal for LDL-C that may require additional testing and treatment, with uncertain marginal gain.

For individuals with elevated triglycerides, both guidelines recommend lifestyle therapy and, if the individuals have high enough risk, statins. ESC/EAS recommends in high-risk patients with diabetes mellitus and with elevated triglycerides despite statin therapy, icosapent ethyl fatty acids at 2 g twice daily. This is based on a randomized controlled trial published after AHA/ACC was released.[4]

ESC/EAS did not list specific factors such as pre-eclampsia and premature menopause for women, as seen in AHA/ACC. Also, in ESC/EAS guidelines, plaque imaging includes carotid and femoral imaging as well as coronary artery calcium scores. The utility of identifying coronary artery calcium equal to 0 is highlighted in AHA/ACC for reclassifying risk downward and deferring statin therapy in many intermediate risk individuals. The absence of carotid plaque does not have comparable negative predictive value.[5]

Both guidelines recommend consideration of apolipoprotein B and LpA risk assessment. AHA/ACC uses these, if measured, as risk-enhancing factors in those at intermediate and borderline risk. ESC/EAS recommends apolipoprotein B in those with high triglycerides, diabetes mellitus, obesity or metabolic syndrome, or very low LDL-C, and indicates it may be preferred over non-HDL-C. ESC/EAS recommends that LpA should be considered in selected patients with a family history of premature CVD and for reclassification in people who are borderline between moderate and high risk. Uniquely, ESC/EAS guideline recommends LpA measurement once in each person's lifetime to identify those with very high inherited LpA levels (>180 mg/dL or >430 nmol/L) which may impart a lifetime ASCVD risk equivalent to that of heterozygous familial hypercholesterolemia. ESC/EAS do not clearly indicate how clinicians and patients address the mild to moderately high LpA values identified with this screening approach.

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