Getting a Grasp of the Guidelines
The new cholesterol guidelines seek to align the guideline recommendations more closely with the evidence. They are designed for the patient and physician to individualize the prescription for better cardiovascular health. This was accomplished by combining the output of two workgroups on lifestyle and risk assessment with the report of the cholesterol panel.1-3
A heart healthy lifestyle is always where the prescription begins, but it may, in higher risk groups, not be enough to reduce the risk of heart attack and stroke. This addresses the fact that nearly one in three Americans die of atherosclerotic cardiovascular disease (ASCVD) and almost 60 percent will have a heart attack or stroke.
The cholesterol guideline recommends statins to reduce the risk of ASCVD in those most likely to benefit. The systematic evidence review of randomized trials was designed to produce a set of guidelines that arose from the evidence. Statins are inexpensive (five of seven are available as generics) and safe if given properly. Strong evidence supports an overall net benefit in four groups of individuals:
- Clinical ASCVD*
- Elevations of LDL-C ≥ 190 mg/dl
- Primary prevention – Diabetes aged 40-75 years with LDL-C 70-189 mg/dl
- Primary prevention – No diabetes with ≥ 7.5 percent 10-year ASCVD risk** aged 40-75 years with LDL-C 70-189 mg/dl
The guideline provides a strategy for determining whether to begin statin therapy in those who are not included in the four statin benefit groups described above, or for whom risk assessment is uncertain. Moderate evidence supports the use of moderate intensity statins in primary prevention in individuals with 5 to < 7.5 percent 10-year ASCVD risk aged 40-75 years with LDL-C 70-189 mg/dl. Additional factors that may increase risk may also inform the treatment decision. They include: LDL C ≥ 160 mg/dL, family history of premature ASCVD; hs-CRP > 2.0; lifetime risk of ASCVD (burden of risk factors); Coronary Artery Calcium score ≥ 300 Agaston units or > 75th percentile for age, sex and ethnicity; or an abnormal Ankle Brachial Index ≤ 0.90.
In primary prevention, the guideline recommends a clinician-patient discussion of the potential for an ASCVD risk reduction benefit and the potential for adverse effects, as well as patient preferences before any statin prescription is prescribed. Here is where clinician judgment regarding other ASCVD risk factors, statin safety issues, and a consideration of patient preferences can inform this decision. Whether or not to write a statin prescription is based on both the 10-year ASCVD risk and this discussion.
It should be noted that routine initiation of statin therapy is not recommended for individuals with New York Heart Association class II-IV heart failure or for those receiving maintenance hemodialysis. Clinical judgment is required to determine if such individuals should receive or continue statin therapy.
The primary prevention 7.5 percent 10-year ASCVD risk threshold was chosen because randomized controlled trial (RCT) evidence strongly supports treatment at this level up to the age of 75 years. For those concerned that risk calculation using the ACC/AHA Pooled Cohort equations might overestimate risk, the panel found benefit for moderate intensity statin therapy in individuals with a five percent to <7.5 percent 10-year ASCVD risk. Importantly, the risk discussion can point to other causes of risk, such as cigarette smoking and hypertension that require immediate attention. However, treatment of blood pressure and smoking cessation do not eliminate increased ASCVD risk over the near term and statin therapy should still be considered. It is worth noting that from 65 to 75 years, age may elevate risk into the statin treatment range without severe elevations of other risk factors. Nonetheless, individuals in this age range are still at increased risk of ASCVD in the 10-year time frame and have been shown to experience significant ASCVD risk reduction benefits without an excess of adverse events with statin therapy. After age 75, comorbidities, patient preferences, and safety considerations play a larger role in the decision to initiate statin therapy for primary prevention.
High-intensity statins lower LDL-C approximately 50 percent and moderate-intensity statins lower LDL-C approximately 30 percent – 50 percent. If tolerated, high-intensity statins are recommended for secondary prevention, those with LDL-C ≥ 190 mg/dl, and may be used in those with or without diabetes aged 40-75 years with a >7.5 percent 10-year ASCVD risk. Moderate-intensity therapy is recommended for secondary prevention patients over 75 years, for primary prevention with < 7.5 percent 10-year ASCVD risk, and in those that cannot tolerate or would experience problems from a high-intensity statin. Caution is recommended when using statins in those with a history of statin intolerance, individuals >75 years of age, those who are taking concomitant medications that alter drug metabolism, those with severe comorbid conditions, or taking drugs for conditions that require complex medication regimens (for example, those who have undergone solid organ transplantation or are receiving treatment for HIV-examples of more severe co-morbid conditions).
Follow-up is different in the new guidelines. The guideline no longer recommends using LDL-C and/or non-HDL-C as treatment targets; nor should they serve as performance measures. Indeed the panel could not find evidence for any specific level of LDL-C as a treatment target. Rather, the focus is on optimal lifestyle and adherence to the appropriate intensity of statin therapy. After the initial lipid assessment and appropriate safety evaluations, a follow-up visit 4-12 weeks later includes an assessment of lifestyle and medication adherence, safety, and a second lipid panel. If the percent LDL-C reduction is known, that information can give the physician clues as to adherence to both statins and lifestyle. In those already on a statin for whom baseline LDL-C is unknown, the panel noted that an LDL-C <100 mg/dl was observed in most individuals receiving high-intensity statin therapy in RCTs, though this is not recommended as a treatment target or performance measure. Patients should be encouraged to keep LDL-C low and improve lipids generally by focusing on an optimal heart-healthy lifestyle. Once satisfactory adherence and LDL-C levels have been established, further assessments every 3-12 months should be performed as clinically indicated. In patients with established adherence, consider monitoring every 12 months.
Safety is reviewed in the guidelines and a management strategy is provided for the patient with mild-moderate or severe muscle complaints, elevated blood glucose and risk of diabetes, as well as less common complaints in patients taking a statin. Routine monitoring of liver function tests is no longer recommended.
Statins are first-line therapy for the secondary and primary prevention of ASCVD. The guidelines do not recommend nonstatins for routine use, but they may be used in certain circumstances to further lower LDL-C in patients receiving the maximally-tolerated dose of statin. Nonstatins are likely to be used in most patients with primary LDL-C ≥ 190 mg/dl. In these individuals, experienced clinicians often use multi-drug therapy to get LDL-C to a lower range. If used, the guideline recommends nonstatin therapy that has been shown in randomized controlled trials to reduce ASCVD events and to be safe. Nonstatin therapy may be appropriate in cases of statin intolerance.
Clinicians may wish to review the clinical vignettes at CardioSource.org/Prevention for case examples of how the guidelines can work in practice. In essence, the focus is less on a specific number and more on evidence based therapy shown to reduce ASCVD events.
The 2013 ACC/AHA cholesterol treatment guidelines were developed to provide evidence-based recommendations for the secondary and primary prevention of ASCVD. Treatment of complex lipid disorders and individuals with comorbidities that would have precluded inclusion in the randomized trials reviewed are beyond the scope of the guideline. Expert clinical judgment will be needed to manage these patients.
Article written by Neil J. Stone, MD, FACC, Jennifer Robinson, MD, MPH and David C. Goff, Jr., MD, PhD. Stone and Robinson are lead authors of the cholesterol guideline, and Goff is lead author of the guideline on the assessment of cardiovascular risk.
* Clinical ASCVD is defined by the inclusion criteria for the secondary prevention statin RCTs (acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin).
** 10-year ASCVD risk is defined as incident nonfatal myocardial infarction, coronary heart disease death, and nonfatal or fatal stroke.
1. Stone N, Robinson J, Lichtenstein A, 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; online ahead of print November 12, 2013.
2. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol; online ahead of print November 12, 2013.
3. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol; online ahead of print November 12, 2013.
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