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

Year Released: 2016

Society: American College of Cardiology


The ACC and AHA in 2013 co-published the Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, along with a companion Guideline on the Assessment of Cardiovascular Risk in asymptomatic individuals.

Those guidelines used independent evidence review from various randomized clinical trials and demonstrated that the majority of data indicated statin drugs provided the most effective and safe form of low-density lipoprotein cholesterol (LDL-C) lowering for atherosclerotic CVD risk reduction.

The reviews helped identify four groups for whom the atherosclerotic CVD (ASCVD) risk reduction significantly outweighed the risk for adverse events:

  1. adults aged 21 years or older with clinical ASCVD;
  2. adults aged 21 years or older with LDL-C ≥190 mg/dL (not due to secondary modifiable causes);
  3. adults aged 40 to 75 years without ASCVD, but with diabetes and LDL-C 70 mg/dL to 189 mg/dL; and
  4. adults aged 40 to 75 years without ASCVD or diabetes, with LDL-C 70 mg/dL to 189 mg/dL, and an estimated 10-year risk for ASCVD of 7.5% or higher (according to Pooled Cohort Equations).

At the time, there were no data supporting the use of nonstatin agents for LDL reduction with the goal of lessening risk for CVD events, but that has changed in the years since, with the publication of trials such as IMPROVE-IT and HPS2-Thrive.

The 2013 cholesterol guideline states that nonstatin therapies may be considered in patients who respond poorly to statins or cannot tolerate optimal doses of them.

Addressing current gaps

The goal of the expert consensus decision pathway committee was to address current gaps in care for LDL-C lowering to reduce ASCVD risk. The committee relied on the evidence used in the 2013 ACC/AHA guideline to provide further recommendations for clinicians and patients concerning the use of nonstatin therapies. Specifically, they aimed to provide practical guidance for situations not covered by the 2013 guideline until subsequent guidelines can review recent scientific evidence, and cardiovascular outcomes trials of new agents for ASCVD risk reduction are completed.

Nonstatin therapies

The 2016 guideline recommends patients and clinicians discuss the benefits, harms and preferences related to nonstatin therapy, and that lifestyle changes, adherence to therapy and response to therapy should be monitored.

Options to consider outside of statin therapies may include a referral to a lipid specialist and registered nutritionist, ezetimibe (Zetia, Merck), bile acid sequestrants and PCSK9 inhibitors such as alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen).

PCSK9 inhibitors are reserved for consideration only in high-risk patients with clinical atherosclerotic CVD or those with familial hypercholesterolemia who have not had adequate LDL reduction on maximally tolerated statin therapy, according to the guidelines.

In the absence of long-term safety and efficacy data, use of PSCK9 inhibitors is not recommended for low-risk patients. Mipomersen (Kynamro, Isis Pharmaceutical/Genzyme), lomitapide (Juxtapid, Aegerion) and LDL apheresis may be considered by lipid specialists for patients with familial hypercholesterolemia.

Read more:

Lloyd-Jones DM, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.03.519

Cardiology Today coverage: https://www.healio.com/cardiology/chd-prevention/news/online/%7b71af6410-948e-4ef2-8b5e-b29f06bd5ede%7d/acc-publishes-consensus-document-on-nonstatin-therapies-for-ldl-reduction

Cardiology Today coverage: https://www.healio.com/cardiology/chd-prevention/news/online/%7B1bf5820f-73c0-4e8a-85e2-3cb74f4e430f%7D/improve-it-ezetimibe-added-to-statin-therapy-improved-cv-outcomes

Cardiology Today coverage: https://www.healio.com/cardiology/chd-prevention/news/online/%7bfed3921e-5387-4b75-abff-eb6ddda7be30%7d/hps2-thrive-analysis-adding-niacin-with-laropiprant-to-statin-reduced-survival-increased-costs