Guidelines For The Treatment Of High Blood Cholesterol

As seen in the Consultant Connection July 2015 Issue
Prepared by Brock Reynolds, PharmD Candidate 2015, Raabe College of Pharmacy, Ohio Northern University
 
In 2013, the American College of Cardiology and American Heart Association (ACC/AHA) published updated guidelines for the treatment of high blood cholesterol, replacing the previous guidelines, the third report of the Adult Treatment Panel III (ATP III). The new guidelines brought about a paradigm shift in treating high cholesterol based on evidence from randomized controlled trials, meta-analyses, and observational studies. This article will briefly review the current cholesterol guidelines focusing on how they differ from the previous guidelines and the main points that health care providers should take away from them.
The biggest and most apparent change in the guidelines was the elimination of the recommendation to treat high cholesterol to specific goal LDL (bad cholesterol) levels. This practice was replaced with recommendations focused on reducing the risk of cardiovascular events such as heart attack and stroke. Previously, it was thought that treating blood cholesterol to a specific goal number was associated with cardiac benefit. For example, ATP III recommended that physicians treat patients to an LDL goal of less than 100 mg/dL or 70 mg/dL for the prevention of cardiovascular events. Because of this practice, it was not uncommon for physicians to use several different classes of cholesterol-lowering medications (such as niacin, bile acid sequestrants, fibrates, etc.) on top of statins to try to achieve a patient’s goal LDL, exposing them to increased risk of side effects. The new ACC/AHA guidelines did not find any evidence in their review of literature to reinforce this practice. They found that reduced cardiovascular risk was associated with specific doses of statins (moderate or high intensity), rather than treating to a specific LDL goal number; this suggests that statins may have additional benefits outside of their ability to reduce LDL cholesterol. Statins inhibit HMG-COA reductase, an enzyme involved in the production of blood cholesterol. The new guidelines define moderate intensity statin therapy as a statin that will potentially lower LDL cholesterol by 30-50% from baseline and high intensity statin therapy as a statin that will potentially lower LDL cholesterol by 50% or more from baseline. Accordingly, the new guidelines no longer recommend non-statin cholesterol lowering therapy, because there was no evidence of cardiovascular risk reduction in treating simply to lower LDL cholesterol numbers.
The new guidelines also outline four major groups of patients that will most likely benefit from statin therapy. These groups include: 
  • Patients with clinical atherosclerotic cardiovascular disease (ASCVD, defined as heart attack, stroke, peripheral vascular disease, or any other disease assumed to be related to atherosclerosis)
  • Patients with an LDL > 190 mg/dL
  • Patients with diabetes, age 40-75, with an LDL of 70-189 mg/dL, and without ASCVD
  • Patients without ASCVD or diabetes with an LDL of 70-189 mg/dL and an estimated 10 year cardiovascular risk of >7.5%
 
For patients in group one who already have clinical ASCVD, high intensity statin therapy is recommended. Patients with an LDL level >190 mg/dL are also recommended to have high intensity statin therapy. Deciding which statin intensity to use in the last two benefit groups can be determined by the patient’s 10-year cardiovascular risk. An ASCVD risk estimator was developed to determine a patient’s 10-year risk of having a cardiovascular event and can be found online or as a free mobile app (https://goo.gl/qGrypd). The risk estimator takes into account the patient’s sex, age, race, total cholesterol, HDL cholesterol, systolic blood pressure, the presence of diabetes, whether or not the patient is treated for hypertension, and if he/she is a smoker. For patients falling into the diabetes benefit group, it is recommended to use a moderate intensity statin unless that patient’s 10-year cardiovascular risk is greater than 7.5%, in which case a high intensity statin is recommended. For patients falling into the fourth benefit group, a moderate or high intensity statin may be used depending on physician and patient judgment. 
The guidelines also make special mention of considerations for patients over the age of 75, as they are at higher risk for developing side effects due to statin therapy. Statin drugs have a fairly common side effect of muscle aches and pains, known as myopathy. Myopathy is even more evident in the elderly population. This side effect, coupled with patient specific factors such as comorbid diseases and taking multiple medications can contribute to decreased quality of life and falls in the elderly. The guidelines do state that in patients over the age of 75 already receiving high intensity statin therapy, it is potentially appropriate to continue therapy, as long as the patient is tolerating a high intensity statin without significant side effects. For patients over the age of 75 being newly started on statin therapy, the guidelines state that moderate intensity statins should be used, even if the patient would otherwise be a candidate for high intensity statins.
In addition to these changes, the new guidelines have also changed the recommended monitoring for both statin therapy and cholesterol in general. A liver enzyme test called an ALT should be performed at baseline and repeated only if symptoms of liver toxicity appear after statin initiation. Creatinine kinase should only be checked in individuals with a history of muscle symptoms, as they are at higher risk for myopathy with statin therapy; creatinine kinase can then be checked if muscle symptoms appear after statin initiation and compared to baseline. LDL cholesterol levels should still be checked at baseline, 4-12 weeks after initiation of therapy, and then every 6-12 months. However, this is not to monitor goal cholesterol levels, but rather to assure that there is an appropriate response to therapy and that the patient is being compliant with their medication and lifestyle modifications. 
These new guidelines offer significant changes in the way we approach treating high cholesterol and cardiovascular disease. The major changes and points to take away include: clinicians are now guided to treat patients with the goal of reducing cardiovascular risk such as heart attacks and stroke, rather than treating to specific blood cholesterol goals; non-statin lipid lowering therapy in general is no longer recommended due to the lack of evidence that they reduce cardiovascular risk when added to statin therapy; four major groups of patients were identified that would benefit the most from statin therapy; a cardiovascular risk estimator was developed to help physicians decide what intensity of statin therapy may be appropriate for specific patients. It’s important to remember that the changes that were made were made based off of evidence found in peer reviewed literature. It may take time for prescribing habits and approaches to treatment reflect the new guidelines since it has been over 10 years since the publication of the last lipid guidelines, but keeping these changes in mind will make the transition easier.
References
1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-2934. doi:10.1016/j.jacc.2013.11.002.
2. ATP III Final Report PDF: Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-421.
3. Mahvan TD, Hilaire ML, Vigil A, et al. Cholesterol Management in Geriatric Patients: New Guidelines. Consult Pharm. 2015;30:68-76.