2018 AHA/ACC Multisociety Cholesterol Guideline vs 2019 ESC/EAS Dyslipidemia Guidelines: 5 Things to Know

Andi Shahu, MD, MHS; David I. Feldman, MD, MPH; Erin D. Michos, MD, MHS, FACC, FAHA, FASE

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June 30, 2021

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4. Both the AHA/ACC and ESC/EAS guidelines base treatment decisions on ASCVD risk, but the ESC/EAS guideline sets LDL-C goals whereas the AHA/ACC guideline has LDL-C thresholds.

The ESC/EAS guidelines have taken the "lower is better" approach by providing LDL-C goals for each ASCVD risk level. In the European guideline, for secondary prevention in patients at very high risk and for primary prevention in patients at very high risk, lipid-lowering therapy should be given with the goal of lowering LDL-C by ≥ 50% from baseline and achieving a target level < 55 mg/dL. High-risk patients should be treated with the aim of lowering LDL-C by ≥ 50% from baseline and achieving a target level < 70 mg/dL. Moderate-risk patients should have a goal of lowering LDL-C to < 100 mg/dL, and low-risk patients should have an LDL-C goal < 116 mg/dL.

Therefore, independent of ASCVD status, if maximal tolerated statin therapy fails to lower a patient's LDL-C below the target level, the ESC/EAS guidelines recommend that clinicians consider the addition of nonstatin therapy. Consequently, under the ESC/EAS guidelines, more primary prevention patients would require add-on therapy with ezetimibe and PCSK9 inhibitors to achieve the specified LDL-C goals compared with patients treated per the AHA/ACC guideline.

In contrast to the ESC/EAS guidelines, the AHA/ACC guideline does not specify target LDL-C goals but rather recommends a threshold-based approach for the addition of nonstatin therapy (ezetimibe and/or PCSK9 inhibitors) to statins, one that applies only for secondary prevention patients with known ASCVD or primary prevention patients with severe hypercholesterolemia. For patients with clinical ASCVD, the addition of ezetimibe could be considered if LDL-C levels remain above a threshold ≥ 70 mg/dL despite maximally tolerated statin therapy. For patients with clinical ASCVD who are also at very high risk, addition of a PCSK9 inhibitor could be considered if LDL-C levels remain above a threshold ≥ 70 mg/dL despite maximally tolerated statin therapy and ezetimibe. For patients with heterozygous familial hypercholesterolemia, the addition of a PCSK9 inhibitor could be considered if LDL-C levels remain above a threshold ≥ 100 mg/dL despite maximally tolerated statin therapy and ezetimibe.

Therefore, in the AHA/ACC guideline, the treatment of primary prevention patients is limited to statin therapy, with no consideration of an LDL-C goal; furthermore, there is no specific recommendation for the addition of a nonstatin lipid-lowering therapy except for patients with heterozygous familial hypercholesterolemia.

5. The AHA/ACC and ESC/EAS guidelines differ in how each utilizes non–LDL-C biomarker targets to assess individual patient risk.

The ESC/EAS guidelines recommend the use of LDL-C targets as well as those for apolipoprotein B (apoB) and non–high-density cholesterol (non–HDL-C) levels. Measurement of apoB and non–HDL-C is recommended for patients at very high risk with other comorbidities, including hypertriglyceridemia, diabetes mellitus, obesity, or very low LDL-C levels, to better stratify ASCVD risk. In this population, the ESC/EAS guidelines recommend targeting an apoB goal < 65 mg/dL or a non–HDL-C goal < 85 mg/dL; however, these targets do not exist for patients at lower ASCVD risk. The ESC/EAC guidelines also recommend measuring Lp(a) at least once in an adult patient's lifetime as a means to help further stratify those who are at high risk for ASCVD, though no specific target level is recommended.

On the other hand, the AHA/ACC guideline generally considers non–LDL-C biomarkers to be risk enhancers — not primary targets — for diagnosis or intervention. For example, the AHA/ACC guideline considers it reasonable to measure apoB in patients with triglyceride levels > 200 mg/dL, even though there is no target apoB level. This guideline also suggests that measurement of Lp(a) is indicated in patients with a family history of ASCVD that cannot be explained by major risk factors. In this case, again, there is no target Lp(a) level; rather, this biomarker simply serves as a risk enhancer in ASCVD risk stratification. The AHA/ACC guideline also states that non–HDL-C levels can be used as an initial screening test or considered as a risk enhancer in cases wherein non–HDL-C levels are 190-219 mg/dL. In addition, the AHA/ACC's guideline recommends starting a PCSK9 inhibitor in very high-risk patients who are on a maximally tolerated statin and ezetimibe and have a non–HDL-C level ≥ 100 mg/dL.

For patients with elevated triglyceride level, both the AHA/ACC and ESC/EAS guidelines recommend statin therapy as first-line treatment for patients with moderate hypertriglyceridemia. To reduce the risk for pancreatitis, both guidelines state that fibrate therapy should be considered for patients whose triglyceride levels remain ≥ 500 mg/dL despite lifestyle modifications.

Regarding the use of icosapent ethyl as an adjunctive therapy for moderately elevated triglyceride levels, the 2018 AHA/ACC guideline was published before the REDUCE-IT trial and thus did not endorse icosapent ethyl for cardiovascular risk reduction. The 2019 ESC/EAS guidelines, however, include a IIa recommendation for use of icosapent ethyl in high or very high-risk patients with triglyceride levels in the range of 135-500 mg/dL despite controlled LDL-C on statin therapy.

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