Role of Nonstatin Therapies for Low-Density Lipoprotein Cholesterol Lowering in Management of Atherosclerotic Cardiovascular Disease Risk

GUIDELINE TITLE: 2016 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for Low-Density Lipoprotein Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk DEVELOPER: American College of Cardiology; endorsed by the National Lipid Association RELEASE DATES: April 1, 2016 (online); July 5, 2016 (print) PRIOR VERSION: NA FUNDING SOURCES: American College of Cardiology (ACC) TARGET POPULATION: Adults 21 years of age and older at risk for atherosclerotic cardiovascular disease (ASCVD). MAJOR RECOMMENDATIONS: The Expert Consensus Panel made recommendations for 4 groups at risk for ASCVD who should already be receiving statin therapy. Guidance is provided on approaches to stressing statin adherence, intensifying lifestyle modifications, evaluating for statin intolerance, and controlling other risk factors prior to considering nonstatin therapies. Once these issues have been addressed, clinicians and patients may consider addition of nonstatin therapies after weighing the amount of LDL-cholesterol (LDL-C) reduction achieved, the potential for additional ASCVD risk reduction, the additional amount of LDL-C lowering that is desired, potential for adverse events, and patient preferences. Based on available evidence of nonefficacy and potential harms, there are no clear indications for the routine use of niacin preparations in any group. All patients should have ongoing monitoring for adherence to medications and lifestyle and LDL-C response to therapy. Nonstatin medications that may be considered and sequence of care are outlined for each of the 4 groups below: 1. Patients with clinical ASCVD: if the patient has stable ASCVD and has not achieved at least 50% reduction in LDL-C on statin (with optional threshold for consideration if LDL-C levels less than 100mg/dL have not been achieved or if baseline LDL-C values are unknown [to convert to micromoles per liter, multiply by 0.0259]), ezetimibe should be considered first. If goals have still not been achieved, consideration of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is reasonable in addition to or in place of ezetimibe. For patients with clinical ASCVD and high risk features, the goal is at least 50% reduction in LDL-C with an optional threshold of LDL-C less than 70mg/dL, with the same recommended treatment sequence. 2. Patients without clinical ASCVD and with primary LDL-C levels of at least 190mg/dL: the recommendation is to achieve at least 50% LDL-C reduction (with an optional threshold of LDL-C less than 100mg/dL) and to consider either ezetimibe or a PCSK9 inhibitor first, depending on the amount of additional LDL-C lowering that is desired. Referral to a lipid specialist and registered dietician-nutritionist is recommended, especially for patients with homozygous familial hypercholesterolemia or baseline LDL-C levels at least 250mg/dL. 3. Patients aged 40 to 75 years without clinical ASCVD and with diabetes: the recommendation is to achieve at least 50% LDL-C reduction (with an optional threshold of LDL-C levels less than 100mg/dL or non-high-density lipoprotein cholesterol levels less than 130mg/dL [to convert to micromoles per liter, multiply by 0.0259]). Ezetimibe is considered the best first agent to consider; a bile-acid sequestrant may be considered for ezetimibe-intolerant patients whose triglycerides are less than 300mg/dL (to convert to micromoles per liter, multiply by 0.0113). Proprotein convertase subtilisin/kexin type 9 inhibitors are not recommended at this time. 4. Patients aged 40 to 75 years without clinical ASCVD or diabetes and with 10-year ASCVD risk of at least 7.5%: for patients treated with moderate-intensity statin, dose escalation to a high-intensity statin should be considered (optional threshold LDL-C levels less than 100mg/dL) or if they have high-risk markers. If goals have not been achieved, consider ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors are not recommended at this time.