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Editor's Note
August 2016

Low-Density Lipoprotein Cholesterol Levels and Statin Treatment—A Moving Target?

JAMA Intern Med. 2016;176(8):1113. doi:10.1001/jamainternmed.2016.2784

Statins are a staple of secondary prevention for individuals with stable cardiovascular disease. However, there is controversy on how to determine the right statin dose, and whether it should be based on low-density lipoprotein cholesterol (LDL-C) levels. Guidelines for secondary prevention in individuals with stable cardiovascular disease differ in recommending a statin intensity goal or a particular LDL-C level (typically <70 mg/dL).1,2 In this issue of JAMA Internal Medicine, Leibowitz et al3 report on more than 31 000 Israeli adults with stable cardiovascular disease and the association between their LDL-C levels with statin use and cardiovascular outcomes. After adjusting for multiple potential confounders, the authors observed that individuals who achieved an LDL-C level of 70 mg/dL or less were no less likely to have major adverse cardiovascular events compared with those who achieved an LDL-C between 70 and 100 mg/dL. Using nonlinear modeling, the authors found that achieving lower LDL-C levels was associated with a decreased risk of cardiovascular events, but only to an LDL-C of roughly 90 mg/dL.

This retrospective study represents an important effort in clarifying goals for long-term statin therapy. The findings suggest that targeting an LDL-C level of less than 100 mg/dL achieves the same cardiovascular risk reduction as more aggressive LDL-C targets, which could help to minimize adverse effects that are more common with higher statin doses needed for lower LDL targets while maximizing benefits. The finding of improved outcomes below a threshold LDL-C level also supports consideration of absolute LDL-C levels instead of relative LDL-C percentage reductions for gauging an adequate response to statin therapy and raises questions about the practice of statin dosing by intensity. The study by Leibowitz et al3 adds important information to the ongoing discussion of the best statin strategy and LDL-C targets to improve outcomes with minimal harms.

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Article Information

Conflict of Interest Disclosures: None reported.

References
1.
Amsterdam  EA, Wenger  NK, Brindis  RG,  et al; ACC/AHA Task Force Members.  2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2014;130(25):e433-e434]. Circulation. 2014;130(25):e344-e426.PubMedArticle
2.
Hamm  CW, Bassand  JP, Agewall  S,  et al; ESC Committee for Practice Guidelines.  ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(23):2999-3054.PubMedArticle
3.
Leibowitz  M, Karpati  T, Cohen-Stavi  CJ,  et al.  Association between achieved low-density lipoprotein levels and major adverse cardiac events in patients with stable ischemic heart disease taking statin treatment [published online June 20, 2016]. JAMA Intern Med. doi:10.1001/jamainternmed.2016.2751.
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