, pooled cohort risk score versus FRS versus biology-based risk assessment). (1) Framingham score, (2) pooled cohort risk score, (3) novel markers Key Question 4 Pharmacotherapy: Statins Ezetimibe Bile acid sequestrants Niacin Fibrates Omega-3 fatty acids Bempedoic acid Key Question 5 Treating to goals with pharmacotherapy: LDL goal of <100 mg/dL or <70 mg/dL and non-HDL goal of <130 mg/dL or <100 mg/dL Low HDL or high TGs (150 499 mg/dL) Key Question 6 Pharmacotherapy: High dose/intensity statins or ezetimibe, PCSK9 inhibitors, bile acid sequestrant, niacin, fibrate, or fish oils added to statins LDL <70 or <100 and non-HDL <100 or 130 mg/dL Intensified treatment Lower LDL or non-HDL goals Key Question 7 Pharmacotherapy: Statin-Associated Muscle Symptom Clinical Index tool, measurement of CK levels assessment for myalgia and risk factors Alternative day statin therapy Switching to a different statin Lowering the dose Combination therapy after dose reduction or a change in drug Optimize vitamin D status using supplements Key Question 8: Stop statin use Key Question 9: Lipid interventions (pharmacologic and non-pharmacologic) Key Question 10 Dietary supplements: Red yeast rice Soluble fiber Garlic Ginger Plant sterols Green tea Niacin Key Question 11: Different dietary therapies (Mediterranean, vegetarian, vegan, low-fat, or DASH diet) Registered dietitian (RD) providing individualized counseling Key Question 12 Physical activity: Resistance training Aerobic exercise (no specification on duration, intensity) c. Comparators Key Question 1: No repeat testing Key Question 2: Previous lab test from same individual over varying time frames Key Question 3: Usual care No formal stratification Different stratification tool Key Question 4: Placebo Another medication class Another medication within the same class A different dose of the same medication Key Question 5: Treating without consideration of reaching lipid goal(s) but based on dosage Key Question 6: Control (less intense or no added therapy) Higher LDL or non-HDL goals Key Question 7: No intervention to improve statin tolerance Key Question 8: Continue statin use Key Question 9: Usual care (placebo, lower intensity statin; or high intensity statin if add-on comparison such as ezetimibe, PCSK9, fibrate, niacin, etc.) 