New Hyperlipidemia Guidelines Include Controversial Recommendations, Subjective Risk Tool

Frank J. Domino, MD

Review

Stone NJ, 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. Circulation. 2013 Nov 12. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a.full.pdf.

Study Methods

The American College of Cardiology (ACC) and American Heart Association (AHA) collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and other stakeholders and professional organizations to develop clinical practice guidelines for the assessment of cardiovascular (CV) risk, lifestyle modifications to reduce that risk, and management of blood cholesterol, weight, and obesity in adults.

Results and Outcomes

The report authors developed recommendations and assigned each one an evidence grade, as annotated below.

1. Patients <75 years old with known atherosclerotic cardiovascular disease (ASCVD) should receive high-intensity statins, such as atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day. [A]
2. Patients >75 years old with known ASCVD may benefit from moderate-intensity statin therapy with atorvastatin 10-20 mg, rosuvastatin 5-10 mg, pravastatin 40-80 mg, simvastatin 20-40 mg, lovastatin 40 mg, fluvastatin 40 mg bid, fluvastatin XL 80 mg, or pitavastatin 2-4 mg, or high-intensity statin therapy. [E]
3. Patients >21 years old with low-density lipoprotein (LDL) >190 mg/dL or triglycerides >500 mg/dL should be evaluated for secondary causes and receive high-intensity statin therapy. [B]
4. Patients aged between 40-75 years of age with diabetes whose 10-year CV risk is ≥7.5% should receive high-intensity statins. [E]
5. Patients aged between 40-75 years of age with diabetes whose 10- year CV risk is <7.5%should receive moderate-intensity statin therapy. [A]
6. Patients aged <40 or >75 years old with diabetes should consider statin therapy. [E]
7. Patients aged between 40-75 years old without ASCVD or diabetes with 10-year CV risk of ≥7.5% should receive moderate- to high-intensity statin therapy. [A]
8. All patients should undergo lifestyle changes consisting of a diet rich in fruit, vegetables, whole grains, fish, low-fat dairy, lean poultry, nuts, legumes, and non-tropical oils, as well as restricted saturated fats, trans fats, sweets, sugar, sweetened beverages, and sodium. All patients should also engage in 40 minutes of aerobic physical activity of moderate to vigorous intensity 3-4 times per week and abstain from tobacco use.

A= Strong evidence to support recommendation, or high certainty based on evidence that net benefit is substantial

B= Moderate certainty based on evidence that net benefit is moderate to substantial, or high certainty that net benefit is moderate

E= Expert opinion, which means “there is insufficient evidence, or evidence is unclear or conflicting, but this is what the Work Group recommends.”

Conclusion

Clinicians should move away from specific cutoffs as goals for treating hyperlipidemia, and instead focus on stratifying patients based upon demographics and CV risk. From those factors, physicians should initiate either high- or moderate-intensity statin therapy, and all patients should engage in aerobic exercise and move from a low-fat diet to a Mediterranean diet, which includes fruits, vegetables, fish, nuts, and non-tropical oils.

Commentary

This guideline is the result of a widely representative group of researchers offering analysis and expert opinion on the best evidence available. Where the best evidence was lacking, the authors chose an aggressive stance with regard to pharmacotherapy for the treatment of hyperlipidemia. Of note, the potential conflicts of interest and disclosures of the panel members and authors occupied approximately 14% of the guideline’s content.

The diagnosis of hyperlipidemia was originally used for diseases with a genetic origin. What some call “indication creep” has led to all patients with elevated total and LDL cholesterol being characterized and diagnosed with hyperlipidemia, and this guideline will advance that situation. Whether the latter group has a disease remains unclear.

Though the researchers’ interpretation of the evidence grades is considered to be subjective and may overestimate the literature base to support their recommendations, the take-home points from this guideline include:

• Strong evidence exists for use of high-intensity statins in patients with known ASCVD.
• Good evidence supports statin use in those with diabetes.
• Strong evidence supports most of the lifestyle recommendations, including aerobic exercise, moving toward more fish and vegetable diets while limiting sweets, and not using tobacco products. The restriction of salt is a reasonable recommendation, but it has only short-term data to support it as a “goal.”
• Conflicting evidence suggests the use of moderate-intensity statin therapy in those who do not have known CVD or diabetes, yet have a 10-year CV risk of ≥7.5%. This is the most controversial of the recommendations. While given an evidence grade of A, this seems to be a stretch of this grade, and it is open to significant debate.

The authors offered their version of a risk calculator that was based upon a combination of data and expert opinion regarding the influence of risk factors on cardiovascular disease. This tool has already generated significant controversy, which led to it being temporarily removed from the ACC and AHA websites for review, though it has since been reinstated online. Although also criticized for shortcomings, other noteworthy calculators include:

The well-known Framingham Risk Calculator, which is based upon the Framingham Cohort Study and uses age, tobacco use, gender, total and high-density lipoprotein (HDL) cholesterol, blood pressure (and if hypertensive, under treatment). However, it excludes diabetes, because when it was last updated, diabetes was considered a risk equivalent; this has been subsequently disproven.

The Atherosclerosis Risk in Communities (ARIC) study’s calculator uses gender, race, cigarette smoking, age, total and HDL cholesterol, systolic blood pressure, and the use of anti-hypertensive medication. It also includes diabetes, which likely makes it more accurate than the Framingham.

The Reynolds Score, which is a less evidence-based tool, includes gender, age, tobacco use, family history of coronary artery disease before age 60, systolic blood pressure, total and HLD cholesterol, and C-reactive protein (CRP) level, although AHRQ states there is “insufficient evidence to use CRP for risk stratification.”

Most critically, all patients should be counseled and encouraged to adopt the tenets of a Mediterranean diet and exercise. Statin use in low-risk populations has only been found to be beneficial in patients who limited their intake of red meats, concentrated carbohydrates, and high-risk oils. As clinical trials of statins include exercise as part of their intervention, we do not know if just taking a statin will result in any clinical benefit without exercise. Additionally, it remains unclear if taking a statin while still smoking cigarettes results in any risk reduction or clinical benefit.

Until the controversy over which risk calculator to use and whether the cutoff of 7.5% in low-risk individuals is appropriate, clinicians should treat all patients with patient-centered counseling about appropriate dietary changes, smoking cessation, and aerobic exercise. For those with known CV disease or diabetes and multiple risk factors, statins should be used.

But for those whose risk is ≥7.5% and have no congenital heart disease (CHD) or diabetes, a patient-centered, informed consent discussion about the pros and cons of drug treatment is needed. To best provide this information, use a risk calculator. First, the patient’s risk is determined in his or her current state without a statin, and then calculated again by using an estimated reduction in cholesterol — say, a 20% reduction in total cholesterol &mdash; to determine the risk if the patient were to take a statin.

Comparing these 2 risk estimates will help patients understand their potential benefits of medication, and allow them an opportunity to make an informed choice about whether or not to initiate statin therapy.

Algorithm

Click the image to download this handy flowchart of the hyperlipidemia guidelines.

About the Author

Frank J. Domino, MD, is Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School in Worcester, MA. Domino is Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins). Additionally, he is Co-Author and Editor of the Epocrates LAB database, and author and editor to the MedPearls smartphone app. He presents nationally for the American Academy of Family Medicine and serves as the Family Physician Representative to the Harvard Medical School’s Continuing Education Committee.