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N Engl J Med 2014; 370:275-278January 16, 2014DOI: 10.1056/NEJMms1314569

On November 12, 2013, updated guidelines for the treatment of high blood cholesterol levels were released by the American College of Cardiology–American Heart Association (ACC-AHA) Task Force on Practice Guidelines.1 This update represents the first major guideline revision since the National Cholesterol Education Program released its Adult Treatment Panel III report in 2002.2 The previous guidelines were widely accepted and applied with relative consistency. In contrast, the new guidelines have already been the subject of controversy, with some observers arguing that some elements of the recommendations are not evidence-based.3 Nevertheless, these recommendations may have a major effect on the clinical practice of lipid management. We therefore provide here a brief practical summary of the current cholesterol guidelines, indicating the area of dispute.

KEY FEATURES OF THE NEW GUIDELINES

The current guidelines represent a substantial departure from previous recommendations, which promoted specific lipid-level goals for patients that were dependent on the level of risk. The new guidelines rely heavily on randomized, controlled trials that largely involved fixed doses of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in patient populations that are at risk for atherosclerotic cardiovascular disease (defined as nonfatal myocardial infarction, death due to coronary heart disease, or nonfatal or fatal stroke).

Using this new approach, the expert panel identified four subgroups of patients for whom the benefit of statins clearly outweighs the risk (Figure 1

FIGURE 1

2013 American College of Cardiology–American Heart Association Guidelines for Use of Statin Therapy in Patients at Increased Cardiovascular Risk.

).4 These groups are patients with

1. clinically evident atherosclerotic cardiovascular disease,

2. primary low-density lipoprotein (LDL) cholesterol levels of at least 190 mg per deciliter,

3. type 1 or type 2 diabetes and an LDL cholesterol level of 70 mg per deciliter or higher, or

4. a 10-year risk of atherosclerotic cardiovascular disease of at least 7.5%, according to the new, publicly available, pooled cohort equations,3 and an LDL cholesterol level of at least 70 mg per deciliter.

In these patient groups, high-intensity statin therapy (designed to reduce LDL cholesterol levels by ≥50%) is generally recommended (Table 1

TABLE 1

High-Intensity and Moderate-Intensity Statin Therapy, According to 2013 American College of Cardiology–American Heart Association (ACC-AHA) Cholesterol Guidelines.

). Moderate-intensity statin therapy (aiming for a reduction of 30 to <50% in LDL cholesterol levels) is recommended for patients who cannot tolerate high-intensity treatment or patients with diabetes and a 10-year risk of atherosclerotic cardiovascular disease of less than 7.5%. Persons receiving statin therapy should be monitored for muscle and hepatic injury and for new-onset diabetes.

An important caveat regarding the new guidelines is that they also identify patients for whom available data do not support statin therapy and for whom no recommendation is made. These groups are patients with

1. an age of more than 75 years, unless clinical atherosclerotic cardiovascular disease is present;

2. a need for hemodialysis; or

3. New York Heart Association class II, III, or IV heart failure.

Finally, the panel noted that it found no evidence to support the use of non-statin cholesterol-lowering drugs, either combined with statin therapy or in statin-intolerant patients.

KEY IMPLICATIONS FOR PRACTITIONERS

Practicing clinicians will see considerable changes in practice patterns as they follow the new cholesterol treatment guidelines, including

1. avoidance of cholesterol-lowering therapy in certain patient groups;

2. elimination of routine assessments of LDL cholesterol levels in patients receiving statin therapy, because target levels are no longer emphasized;

3. avoidance of non-statin LDL cholesterol–lowering agents in statin-tolerant patients;

4. more conservative use of statins in patients older than 75 years of age who have no clinical atherosclerotic cardiovascular disease;

5. diminished use of surrogate markers such as C-reactive protein or calcium scores; and

6. the use of a new risk calculator that is certain to target larger numbers of patients for statin treatment.

We have provided some examples of patients with various risk-factor profiles, along with the consequent recommendations for therapy based on use of the new risk calculator (Table 2

TABLE 2

Case Examples of Application of 2013 ACC-AHA Cholesterol Guidelines.

).

Ridker and Cook3 have raised concern about the new risk calculator, which is based on data derived from several large cohort studies. The risk calculator itself has not been prospectively tested for its accuracy in predicting cardiovascular risk. On the basis of comparisons with findings in several large cohorts of persons without current atherosclerotic cardiovascular disease, the new risk calculator appears to overestimate observed risks. The guideline developers, however, note that the cohorts examined by Ridker and Cook may not be appropriate for assessing the accuracy of the risk calculator for two reasons. First, these cohorts include volunteers, who are likely to be healthier than the population as a whole. Second, patients in these cohorts have received modern therapies for reducing cardiovascular risk, thus altering the natural history of the disease.

Overall, the current ACC-AHA recommendations regarding lowering cholesterol levels will move treatment toward statins and deemphasize other agents for a broader range of patients than the previous recommendations did. There is likely to be considerable interest in prospectively testing the new risk calculator in multiple groups of various ethnic backgrounds to substantiate its relevance as a foundation for the primary prevention of atherosclerotic cardiovascular disease.