2013 ACC/AHA Cholesterol Guideline: A New Paradigm Supported by More Evidence | Journal Scan

Study Questions:

How was the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline developed, and what new evidence supports the guideline recommendations?


The 2013 ACC/AHA cholesterol guideline was a major paradigm shift and was criticized by some experts who preferred the low-density lipoprotein cholesterol (LDL-C) treat-to-target strategy promoted by prior guidelines. Other concerns were potential biases of some of the committee members, too low of a risk threshold of 7.5% for treatment likely leading to excessive use of statins, and questions regarding the reliability of the cohorts used to derive the primary prevention risk calculators. This review describes the methodology used to develop the guidelines, the management recommendations, and the evidence supporting them, while addressing many of the criticisms. An extensive body of evidence from randomized clinical trials supports the new risk-based approach. This review includes two outcome trials not available prior to the guideline publication.


The 2013 cholesterol guideline better identifies high-risk patients with a greater burden of atherosclerosis and avoids treating those at lower risk with little atherosclerosis than previous risk predictors; its application is estimated to prevent up to 450,000 more atherosclerotic cardiovascular disease (ASCVD) events over 10 years compared to following prior management algorithms. It emphasizes the importance of healthy lifestyle and is designed to assist clinicians and patients with recommendations that are based on risk-benefit from multiple randomized controlled trials when considering whether to initiate statins, stressing as appropriate patient preferences. The emphasis is on intensity of statin therapy with high-intensity statin (≥50% lowering of LDL-C) for those with ASCVD, LDL-C >190 mg/dl, and diabetes or nondiabetes with a 10-year risk of at least 7.5%. Intermediate dosing (30-<50% reduction in LDL-C) is recommended for those unable to tolerate higher doses, those with diabetes and nondiabetes with LDL-C 70-180 mg/dl, age 40-75 years, and 5% to <7.5% 10-year risk. For those younger than 40 or older than 75 years with an LDL-C <190 mg/dl and/or <5% 10-year risk, additional factors such as family history, lifetime ASCVD risk, abnormal coronary calcium score, ankle-brachial index (ABI), or high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/dl can be used to guide treatment decisions. It also recommends regularly monitoring LDL-C levels to assess adherence to lifestyle and drug therapy, and adjusting treatment based on achieving the expected LDL reduction response to therapy and adverse events. Nonstatins shown to reduce ASCVD events when added to statin therapy, and that have an acceptable margin of safety in randomized controlled clinical trials, are preferred. Ezetimibe has now been shown to meet this standard, and would be particularly valuable to add to statins in the very high-risk patients regardless of LDL-C and dose of statins. There is no benefit, and potential harm, when adding niacin to statin therapy. Criticism that the pooled cohort equations developed for the 2013 guideline were not accurate in certain populations was accepted, with the contention that it was more representative of the general US white and African American populations.


The concept of net benefit introduced in the 2013 ACC/AHA cholesterol guideline identifies patients most likely to benefit from statin therapy to reduce ASCVD risk. Net benefit, incorporating the absolute ASCVD risk of a patient and the relative reduction in ASCVD risk based on the magnitude of LDL-C reduction from the addition of a nonstatin, can be used when considering whether to add ezetimibe or another LDL-C lowering drug.


The experts and clinicians who disagreed with the 2013 ACC/AHA guideline risk assessment and treatment strategy will probably not be influenced by this article. One reasonable argument is that the new guideline remains overly complicated (despite being more streamlined than prior guidelines). Additionally, the use of other risk predictors such as hs-CRP, lipoprotein (a), ABI, and family history are given equal status as the coronary artery calcium score, which is likely of much greater additive independent risk prediction value in primary prevention to guide treatment decisions, as reported in the US Multi-Ethnic Study of Atherosclerosis (MESA). The guideline does appropriately acknowledge existing knowledge gaps (and the need for providers to tailor care on an individual basis in these cases) and that ongoing clinical trials will lead to a rapid evolution and need for updating of the guideline.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Algorithms, Ankle Brachial Index, Anticholesteremic Agents, Atherosclerosis, Azetidines, C-Reactive Protein, Calcium, Cardiovascular Diseases, Cholesterol, Cholesterol, LDL, Coronary Vessels, Diabetes Mellitus, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Life Style, Lipoprotein(a), Lipoproteins, LDL, Niacin, Primary Prevention, Risk, Risk Assessment, Secondary Prevention

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