ACC Publishes Guidelines for Non-Statin Therapies Save

The American College of Cardiology has released its expert consensus guidance regarding the use of non-statin therapies to lower cholesterol in high-risk patients.

In 2013, ACC/American Heart Association published a Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. This is an addendum to the treatments (non-statin) not covered in that guideline.

The new document recommends looking first at lifestyle issues, including diet, regular exercise and smoking avoidance, followed by statin therapy. 

In addition, there are new FDA-approved non-statin therapies, monoclonal antibodies, proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, which have been shown to dramatically reduce low-density lipoprotein cholesterol levels over and above statin therapy. Additionally, recent publication of the HPS2-THRIVE (examining niacin) and IMPROVE-IT (examining ezetimibe) trials has provided new evidence about the addition of non-statin therapies to statins.

The writing committee supports consideration of adding ezetimibe 10 mg daily as the first non-statin agent for many higher-risk patient groups, based upon the benefits in terms of atherosclerotic cardiovascular disease outcomes and demonstrated safety of ezetimibe in patients with acute coronary syndrome treated with ezetimibe-simvastatin versus simvastatin monotherapy.

However, they found that there are no clear indications for the routine use of niacin preparations as additional non-statin therapies, and therefore, do not recommend niacin for the situations discussed in the document.  

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

“Before initiation of combination therapy, it is imperative for clinicians and patients to engage in a discussion that includes the potential for net benefit, including absolute atherosclerotic cardiovascular disease risk-reduction benefits and potential harms, prescribing considerations and patient preferences for treatment.”

The algorithms in this expert consensus decision pathway for consideration of the addition of non-statin therapies to statin therapy begin with the assumption that the patient is in one of the four evidence-based statin benefit groups identified in the 2013 ACC/AHA cholesterol guideline:

1. patients with clinical atherosclerotic cardiovascular disease;
2. patients with LDL-C ≥190 mg/dL, not due to secondary causes;
3. patients aged 40-75 years with diabetes mellitus and LDL-C 70-189 mg/dL; and
4. patients aged 40-75 years with no diabetes but with LDL-C 70-189 mg/dL and predicted 10-year atherosclerotic cardiovascular disease risk ≥7.5%.

For other groups of patients, care should be individualized. Each algorithm provides a suggested clinical workflow for consideration of the addition of non-statin therapies to evidence-based statin therapy.

Critical to the decision process for use of additional non-statin therapies in selected high-risk patients is the definition of thresholds of LDL-C, in terms of percentage reduction and absolute values, for consideration of net atherosclerotic cardiovascular disease risk-reduction benefit. The writing committee emphasizes that these are not firm triggers for adding medication but factors that may be considered within the broader context of an individual patient’s clinical situation.

Additional considerations in the initiation of non-statin therapies include 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, according to the document.