American College of Cardiology
American College of Cardiology
April 02, 2016
3 min read

ACC publishes consensus document on nonstatin therapies for LDL reduction

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CHICAGO — A new expert consensus statement from the American College of Cardiology on nonstatin therapies recommends trying lifestyle and statin therapies before nonstatin medical therapies in patients who require LDL lowering to manage CVD risk.

The document, endorsed by the National Lipid Association, was discussed at the American College of Cardiology Scientific Session and published in the Journal of the American College of Cardiology.

“While evidence-based statin therapy remains the first-line standard of care for patients at risk for atherosclerotic [CVD], clinicians and patients may seek firmer and more specific guidance on adequacy of statin therapy and whether or when to use nonstatin therapies if response to statins is deemed inadequate,” writing committee chair Donald M. Lloyd-Jones, MD, ScM, FACC, chair of the department of medicine and Eileen M. Foell professor of heart research at Northwestern University Feinberg School of Medicine said in a press release.

Donald Lloyd-Jones

Donald M. Lloyd-Jones

Discussion necessary

Before combination therapy is initiated, “it is imperative for clinicians and patients to engage in a discussion that includes the potential for net benefit, including absolute atherosclerotic [CVD] risk-reduction benefits and potential harms, prescribing considerations and patient preferences for treatment,” Lloyd-Jones said in the release.

The document is geared toward patients who meet at least one of the four criteria for statin therapy in the ACC/American Heart Association 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: clinical atherosclerotic disease; LDL ≥ 190 mg/dL; age 45 to 70 years with diabetes and LDL 70 mg/dL to 189 mg/dL; or predicted 10-year atherosclerotic CVD risk ≥ 7.5%.

According to the document, at the time the cholesterol guideline was published, there were no data supporting 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 studies such as IMPROVE-IT and HPS2-THRIVE. The cholesterol guideline states that nonstatin therapies may be considered in patients who respond poorly to statins or cannot tolerate optimal doses of them.

In the new document, the writing committee listed the following factors to be considered in patients from the four groups that can benefit from statin therapy: adherence, lifestyle factors, intolerance of statins, how well other risk factors are controlled and the percentage LDL reduction that should be achieved (a specific LDL target may be considered). They added that there should be a discussion between clinicians and patients on benefits, harms and preferences related to nonstatin therapy, and that response to therapy, lifestyle changes and adherence should be monitored.

Nonstatin options

If it is decided that a nonstatin therapy should be pursued, options to consider include referral to a lipid specialist and registered dietician nutritionist, ezetimibe (Zetia, Merck), bile acid sequestrants and PCSK9 inhibitors such as alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen). The 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 Lloyd-Jones and colleagues, who noted that 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, Lloyd-Jones and colleagues wrote.

An important part of the decision-making process is LDL percentage reduction and target thresholds, but these should not be considered automatic triggers for adding medication, instead factors to consider in the overall context of an individual’s clinical situation, the authors wrote. – by Erik Swain


Lloyd-Jones DM. Dyslipidemia Combo-Therapy: A Framework for Clinical Decision-Making. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.

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

Disclosure: Lloyd-Jones reports no relevant financial disclosures. See the full document for a list of the relevant financial disclosures of the other authors and reviewers.