Review of the US and European literature indicates that most patients at high risk for atherosclerotic cardiovascular disease (ASCVD are not treated with high-intensity statins, despite strong clinical-trial evidence of maximal statin benefit. High-intensity statins are recommended for 2 categories of patients: those with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD. Most patients with ASCVD are candidates for high-intensity statins, with a goal for low-density lipoprotein cholesterol reduction of 50% or greater. A subgroup of patients with ASCVD are at very high risk and can benefit by the addition of nonstatin drugs (ezetimibe with or without bile acid sequestrant or bempedoic acid and/or a proprotein convertase subtilisin/kexin type 9 inhibitor). High-risk primary prevention patients are those with severe hypercholesterolemia, diabetes with associated risk factors, and patients aged 40 to 75 years with a 10-year risk for ASCVD of 20% or greater. In patients with a 10-year risk of 7.5% to less than 20%, coronary artery calcium scoring is an option; if the coronary artery calcium score is 300 or more Agatston units, the patient can be up-classified to high risk. If high-intensity statin treatment is not tolerated in high-risk patients, a reasonable approach is to combine a moderate-intensity statin with ezetimibe. In very high-risk patients, proprotein convertase subtilisin/kexin type 9 inhibitors lower low-density lipoprotein cholesterol levels substantially and hence reduce risk as well.
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