Synopsis of 2018 AHA/ACC/Multisociety Cholesterol Guideline

Grundy SM, Stone NR, on behalf of the Guideline Writing Committee for the 2018 Cholesterol Guidelines.
2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline. Ann Intern Med 2019;170:779-783.

The following are key points to remember from this synopsis of the 2018 American Heart Association (AHA)/American College of Cardiology (ACC)/Multisociety Cholesterol Guideline:

  1. The 2018 AHA/ACC guideline update on cholesterol management differs significantly from the 2013 version. Among the major changes includes a friendly risk assessment tool for primary prevention of atherosclerotic cardiovascular disease (ASCVD) based on high-quality observational studies known collectively as the pooled cohort equation (PCE). The recommendations are based on updated systematic reviews and meta-analysis of randomized controlled trials focusing on statins and introducing the supplement value of nonstatins in statin-intolerant and very high-risk patients, including ezetimibe and protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
  2. For primary prevention, assess ASCVD risk in each age group and emphasize adherence to heart-healthy lifestyle. In children and adolescents, diagnose familial hypercholesterolemia and treat with statins. In age 20-39 years, estimate lifetime risk and emphasize intensive lifestyle efforts for those at high risk, and in all age groups, identify and intensify diet and exercise for the metabolic syndrome.
  3. Use maximally tolerated statin dosing in secondary prevention of ASCVD. Expect a 50% reduction in low-density lipoprotein cholesterol (LDL-C) with high dosing of high-intensity statins. The lower the reduction in LDL-C with statins, the greater the risk reduction. In patients at very high risk for ASCVD defined as multiple major ASCVD events, or 1 major event and multiple high-risk conditions, consider nonstatin medication. In these very high-risk patients with an LDL-C ≥70 mg/dl, it is reasonable to add 10 mg of ezetimibe. When levels remain above these thresholds, adding a PCSK9 inhibitor is reasonable, although the cost-effectiveness has been low.
  4. Severe primary hypercholesterolemia often begins in childhood. In patients with primary severe hypercholesterolemia defined as an LDL-C >190 mg/dl, it is not necessary to calculate the 10-year ASCVD event risk. Maximally tolerated statins are recommended to reduce the LDL-C to <100 mg/dl. If not achieved, it is reasonable to add ezetimibe. For those with multiple risk factors for ASCVD events, it is reasonable to add a PCSK9 inhibitor.
  5. In adults ages 40-75 years with diabetes and LDL-C ≥70 mg/dl, consider a moderate-intensity statin without calculating 10-year risk. In those with multiple risk factors or ages 50-75 years, use a high-intensity statin to reduce LDL-C by ≥50%.
  6. A clinician–patient discussion should be conducted in persons ages 40-75 years with review of major risk factors including smoking, hypertension, LDL-C level, and hemoglobin A1c if indicated. Consider the calculated 10-year risk of ASCVD events, and risk-enhancing factors that would influence more intense therapies. Among considerations include cost/benefit and adverse effects of statins.
  7. In adults ages 40-75 years without diabetes and LDL-C ≥70 mg with a 10-year ASCVD risk of ≥7.5%, use moderate-intensity statins. Low risk for ASCVD events is defined as <5%, borderline is 5-7.4%, intermediate 7.5-19.9%, and high risk ≥20%. The guideline recommends high-intensity statins in the high-risk group, and evidence supports statins when 10-year risk is ≥5%. Patient preference for statin and statin intensity should always be a consideration.
  8. The decision for primary prevention in adults ages 40-75 years should be facilitated by risk-enhancing factors, which when present in intermediate-risk persons, favors statins. These are stable factors that increase risk and are associated with ASCVD and not included in the PCE risk calculator. These include family history of premature ASCVD, LDL-C ≥160 mg/dl, metabolic syndrome, chronic kidney disease, history of pre-eclampsia or premature menopause, chronic inflammatory disorders, triglycerides persistently >175 mg/dl, high-risk ethnic groups such as South Asians, elevation of apolipoprotein B >130 mg/d, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/dl, or higher lipoprotein (a) >50 mg/dl (especially those with premature ASCVD), or reduced ankle-brachial index.
  9. Coronary artery calcium (CAC) scoring improves risk stratification. In adults without diabetes ages 40-75 years with LDL-C 70-189 mg/dl and a 10-year risk of 7.5-19.9% with the PCE who are uncertain about statin therapy, if the CAC score = 0, statins may be withheld or delayed with the exception of smokers, or those with a family history of premature ASCVD or diabetes. A CAC score of 1-99 units favors statins, especially in persons ages >55 years. For any patient with a CAC score of ≥100 or above the 75th percentile for age/gender, statins are indicated unless deferred after the clinician–patient risk discussion.
  10. Follow-up for adherence and adequacy of response to changes in lifestyle and medication is suggested between 4 and 12 weeks after initiation or dosage change in statins and then repeated every 3-12 months as needed.
  11. The certainty of statin intolerance is difficult. The guideline suggests the term ‘statin-associated side effects,’ which acknowledges that placebo-controlled trials find a significant number of those with side effects are on placebo. With this in mind, it is important to discuss the potential of side effects, that not all statins are alike, and that dose adjustment with addition of nonstatins may be very effective. Statins are associated with a modest increase in diabetes, particularly in those with the metabolic syndrome and prediabetes. This should not be a reason for withholding or discontinuing the statins.
  12. The PCE for 10-year risk estimates have been derived with US cohorts, which together reflect the diverse population, but in some cases may overestimate risk of ASCVD. Cohorts where risk may be overestimated include younger persons, those with healthy lifestyle, higher level education and higher socioeconomic status, and certain ethnic groups. In these circumstances, the clinician can be helped by risk enhancers, CAC score, and other risk estimators that incorporate the hsCRP or CAC score.

Keywords: Apolipoproteins B, Atherosclerosis, Cholesterol, Cholesterol, LDL, Cost-Benefit Analysis, C-Reactive Protein, Diabetes Mellitus, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hypertension, Life Style, Lipoproteins, Menopause, Premature, Metabolic Syndrome, Pre-Eclampsia, Primary Prevention, Proprotein Convertases, Renal Insufficiency, Chronic, Risk Assessment, Risk Factors, Smoking, Triglycerides

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