Expert Consensus on Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk

Lloyd-Jones DM, Morris PB, Ballantyne CM, et al.
2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2016;Apr 1:[Epub ahead of print].

The following are important points to remember about the 2016 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for Low-Density Lipoprotein Cholesterol (LDL-C) Lowering in the Management of Atherosclerotic Cardiovascular Disease (ASCVD) Risk:

  1. The ACC Expert Consensus Decision Pathway was created to address current gaps in recommendations for LDL-C lowering to reduce ASCVD in high-risk subsets based on recent clinical trial evidence.
  2. The 2013 ACC/American Heart Association (AHA) cholesterol guideline identified four major statin benefit groups for ASCVD risk-reduction: 1) patients ≥21 years of age with clinical ASCVD; 2) adults ≥21 years of age with LDL-C ≥190 mg/dl (not due to secondary modifiable causes); 3) adults aged 40-75 years without ASCVD, but with diabetes and with LDL-C 70-189 mg/dl; and 4) adults aged 40-75 years without ASCVD or diabetes, with LDL-C 70-189 mg/dl, and an estimated 10-year risk for ASCVD of ≥7.5%, as determined by the Pooled Cohort Equations.
  3. Recommendations in the 2013 guideline included using either high- or moderate-intensity statin therapy for primary and secondary prevention scenarios, with dose adjustments as necessitated for adverse effects, advanced age, drug-drug interactions, or comorbidities.
  4. The current Expert Consensus Decision Pathways rely on the evidence base established by the 2013 guideline, and incorporate newer clinical trial data on niacin, ezetimibe, and the recently approved PCSK9 inhibitors, alirocumab and evolocumab. The 2013 guideline provided a framework for addition of non-statin therapies that the current Expert Consensus Panel has used to provide more detailed recommendations for specific patient scenarios.
  5. The Expert Consensus Panel addressed three questions, including: 1) In what patient populations should non-statin therapies be considered? 2) In what situations should non-statin therapies be considered, i.e., when is the amount of LDL-C lowering (percent LDL-C reduction or LDL-C range achieved on therapy) less than anticipated, less than desired, or inadequate, and which treatment options should be considered in patients who are truly statin intolerant? 3) If non-statin therapies are to be added, which agents or therapies should be considered and in what order?
  6. All pathways for non-statin therapy recommendations include assuring that the patient is following a healthy lifestyle.
  7. Consistent with the recommendations of the 2013 guideline, fasting LDL-C levels should be regularly assessed after initiation of lipid-lowering treatment and every 3-12 months thereafter as indicated.
  8. The approach to suspected statin intolerance should include temporary discontinuation of statin therapy, lower dosing, re-challenge preferably with 2-3 statins of differing metabolic pathways, and intermittent (1-3x weekly) dosing of long half-life statins.
  9. In selected high-risk patients, such as those with existing ASCVD or LDL-C ≥190 mg/dl, use of non-statins may be considered if maximally tolerated statin therapy has not achieved >50% reduction in LDL-C from baseline.
  10. The pathways also provide guidance on other factors that should be considered regarding the addition of non-statin therapies, including the absolute LDL-C level achieved, the extent of available scientific evidence for safety and tolerability, potential for drug-drug interactions, efficacy of additional LDL-C lowering in ASCVD event reduction, cost, convenience and medication storage, pill burden, route of administration, potential to jeopardize adherence to evidence-based therapies, and importantly, patient preferences. The Expert Consensus Panel emphasizes that LDL-C levels are not firm triggers for adding medication, but they are factors that may be considered within the broader context of an individual patient’s clinical situation.
  11. Referral to a lipid specialist and registered dietitian may be considered for higher-risk patients with statin intolerance, and is strongly encouraged for patients with familial hypercholesterolemia.
  12. Ezetimibe is the first non-statin medication that should be considered in most of the patient scenarios, given its safety and tolerability, as well as demonstrated, though modest, efficacy when added to moderate-dose statin in one trial of patients with acute coronary syndrome.
  13. Bile acid sequestrants (BAS) may be considered as second-line therapy for patients in whom ezetimibe is not tolerated, but they should be avoided in patients with triglycerides >300 mg/dl.
  14. Alirocumab and evolocumab may be considered if the goals of therapy have not been achieved on maximally tolerated statin and ezetimibe in higher-risk patients with clinical ASCVD or familial hypercholesterolemia. Given the lack of long-term safety and efficacy data on these agents, they are not recommended for use in primary prevention patients in the absence of familial hypercholesterolemia.
  15. For patients with homozygous hypercholesterolemia (HoFH), referral to a lipid specialist is strongly recommended with statins, and non-statins including ezetimibe, BAS, with consideration for use of lomitapide, mipomerson, and LDL apheresis as necessary. LDL-apheresis is also approved for heterozygous FH.

Keywords: Atherosclerosis, Bile Acids and Salts, Cardiovascular Diseases, Cholesterol, LDL, Diabetes Mellitus, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Lipids, Metabolic Syndrome, Niacin, Primary Prevention, Risk Reduction Behavior, Secondary Prevention, Triglycerides

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