Three Reasons to Abandon Low-Density Lipoprotein Targets:

Sponsoring organization: American College of Cardiology/American Heart Association (ACC/AHA)

Target Population: Primary care providers, cardiologists

Background and Objective

To guide clinicians in treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.

Key points

— Treating to LDL cholesterol targets is no longer recommended; rather, clinicians should determine whether a patient falls into one of four mutually exclusive high-risk groups and should initiate statin therapy as follows:

  • Patients with clinical atherosclerotic cardiovascular disease (ASCVD) should receive high-intensity (age, <75) or moderate-intensity (age, ≥75) statin therapy.
  • Patients with LDL cholesterol levels ≥190 mg/dL should receive high-intensity statin therapy.
  • Diabetic patients aged 40–75 with LDL cholesterol levels of 70–189 mg/dL and without clinical ASCVD should receive at least moderate-intensity statin therapy (and possibly high-intensity statin therapy when estimated 10-year ASCVD risk is ≥7.5%).
  • Patients without clinical ASCVD or diabetes but with LDL cholesterol levels of 70–189 mg/dL and estimated 10-year ASCVD risk ≥7.5% should receive moderate- or high-intensity statin therapy.

— High-intensity statin therapies are atorvastatin (40–80 mg) or rosuvastatin (Crestor; 20–40 mg). Moderate-intensity statin therapies include atorvastatin (10–20 mg), rosuvastatin (5–10 mg), simvastatin (20–40 mg), pravastatin (40–80 mg), and several others.

— With few exceptions, use of lipid-modifying drugs other than statins is discouraged.

— Ten-year ASCVD risk — which includes both coronary events and stroke — is determined using online calculators that can be accessed through the AHA and ACC websites. For further discussion of the new risk-assessment tool, see NEJM JW Gen Med Nov 12 2013 [2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk PDF at JACCPubMed® abstract]

What's Changed

This guideline is designed explicitly to replace the widely used ATP3 guideline from the National Heart, Lung, and Blood Institutes, last updated in 2004. The obvious major change is that clinicians now are directed to initiate either moderate-intensity or high-intensity statin therapy for patients who fall into the four aforementioned categories, without titration to a specific LDL cholesterol target. Measuring lipids during follow-up of drug-treated patients is done to assess adherence to treatment and not to see whether a specific LDL cholesterol target has been achieved.


This guideline represents a paradigm shift for most clinicians and patients. The rationale for abandoning LDL cholesterol targets is that randomized trials showing benefits of statins generally have examined fixed-dose statin therapy, rather than titrated therapy, to achieve prespecified LDL cholesterol goals. Additionally, some drugs that “improve” the lipid profile (a surrogate endpoint) do not improve clinical outcomes, and statins are thought to exert benefit through pleiotropic effects apart from LDL cholesterol–lowering. The 7.5% risk threshold for primary prevention was selected based on analyses suggesting that benefit from treatment emerges at this threshold. The guideline writers do acknowledge that some patients do not tolerate statins (and might require treatment with lower doses) and that patient preferences for drug therapy should be discussed, particularly in primary prevention. However, the authors do not discuss drug costs: For some patients, the out-of-pocket cost of a high-intensity statin (including generic atorvastatin), compared with the cost for generic simvastatin or pravastatin, is a problem. An essay published last year, entitled “Three reasons to abandon low-density lipoprotein targets,” is a concise and readable analysis of the perspective embodied by this new guideline. (Circ Cardiovasc Qual Outcomes 2012; 5:2). [Cir Cardiovasc Qual Outcomes article PDF | PubMed® abstract]


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