The 2013 ACC/AHA Cholesterol Guidelines One Year Later: What Do We Know and Where to Go From Here

It has now been over a year since the release of the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the management of cholesterol were published.1 A common initial assumption was that these guidelines would substantially increase statin eligibility, but is that actually the case? The purpose of this editorial is to review the data regarding the impact of the ACC/AHA cholesterol guidelines on statin eligibility in the U.S. and consider potential future directions for research.

Compared to the prior Third Adult Treatment Panel (ATP III) guidelines,2 the ACC/AHA guidelines abandon low-density lipoprotein cholesterol (LDL-C) targets and instead rely largely on absolute cardiovascular risk to determine eligibility for statin therapy. This paradigm shift to a risk-based approach is evidence-based and had been endorsed by multiple experts prior to the release of the guidelines.3-5 The guidelines describe four groups of individuals presumed to be at elevated risk and, therefore, most likely to benefit from statin therapy (clinical cardiovascular disease [CVD], individuals with diabetes, an LDL-C >190mg/dl, or an absolute CVD risk >7.5%). The guidelines make it clear that meeting the absolute CVD risk criteria should stimulate a risk-based patient-provider discussion as opposed to a strict mandate for statin therapy.

Using data from the National Health and Nutrition Examination Surveys (NHANES), the potential effect of the ACC/AHA guidelines on the estimated 115 million adults in the U.S. between ages 40-75 years was evaluated by Pencina et al.6 They estimated that, compared to ATP III, 12.8 million additional U.S. adults (56 million total adults) are eligible for statin therapy according to ACC/AHA guidelines. The vast majority of this increase (10.4 million of the 12.8 million) is in adults without known diabetes or CVD. An age-stratified analysis suggested that the vast majority of adults over age 65 years are now statin eligible, largely due to the fact that the Pooled Cohort Equations risk calculator used to determine CVD risk is heavily driven be age, and age is one of the most important risk factors for CVD.

Analyzing data from the Atherosclerosis Risk in Communities (ARIC) Study, a recent analysis has lent further support to the strong role played by age in the determination of ASCVD risk.7 In a sample of 6,088 ARIC participants with data from study visit 5 (2011-2013), 3,125 were between the ages of 66-75 years, of which 24% had CVD, 22% had diabetes, 1% had an LDL-C >190 mg/dl, and 50% had a calculated 10-year CVD risk of >7.5%. Therefore, 97% of individuals between the ages of 66-75 years included in the analysis met one of the four major criteria for statin therapy, whereby, a risk benefit discussion should happen between the patients and the health care provider. This is a substantial increase compared to the 70% that qualified according to the ATPIII guidelines. Of the 97% who qualified for statin therapy, 50% were taking a statin and only 9% were on a statin that would be considered “high-intensity” by the ACC/AHA guidelines. Another recent analysis used data from the National Cardiovascular Data Registry® (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) Registry® to examine the potential implications of the ACC/AHA guidelines on the use of lipid lowering therapy in contemporary cardiology practices.8 In a cohort of over 1.1 million patients cared for in cardiology clinics, 96.1% met one of the four criteria for statin eligibility and 32.4% of those patients were not on statin therapy.

Multiple questions about the ACC/AHA guidelines remain and require further research. For instance, what are the implications of including stroke as part of the Pooled Cohort Equations risk calculator? Statin therapy has been shown to reduce ischemic stroke, but up to 40% of strokes are not atherosclerotic in etiology.9,10 Also, what is the optimal role for additional risk stratification, such as the use of coronary artery calcium (CAC) testing? A CAC score of zero has shown to be associated with a very low rate of CVD events, including in individuals with multiple CVD risk factors and older age.11-13 In addition to identifying a group of high-risk individuals (CAC >300 or >75th percentile for age and gender), could CAC be used to down classify individuals who have a >7.5% CVD risk but have CAC = 0? Finally, how should the results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), which demonstrated a small but significant reduction in CVD events with use of ezetimibe in addition to simvastatin compared to simvastatin alone, be integrated with the approach recommended by the ACC/AHA guidelines.14

In conclusion, the data are quite clear that the application of the ACC/AHA guidelines will lead to an increase in statin eligibility in middle-aged adults, especially in older individuals and those without known heart disease or diabetes. Further research is needed on the optimal role of further risk stratification, the optimal approach for allocating statins for primary prevention of CVD, and the role of non-statin medications for the treatment of cholesterol and the prevention of CVD.

References:

  1. Stone NJ, Robinson J, Lichtenstein AH, 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 2014;63:2889–2934.
  2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
  3. Gaziano JM, Gaziano TA. Simplifying the approach to the management of dyslipidemia. JAMA 2009;302:2148-9.
  4. Hingorani AD, Psaty BM. Primary prevention of cardiovascular disease: time to get more or less personal? JAMA 2009;302:2144-5.
  5. Hayward RA, Krumholz HM. Three reasons to abandon low-density lipoprotein targets: an open letter to the Adult Treatment Panel IV of the National Institutes of Health. Circ Cardiovasc Qual Outcomes 2012;5:2-5.
  6. Pencina MJ, Navar-Boggan AM, D’Agostino RB, et al. Application of New Cholesterol Guidelines to a Population-Based Sample. N Engl J Med 2014;370:1422-31.
  7. Miedema MD, Lopez FL, Blaha MJ, et al. Eligibility for Statin Therapy According to New Cholesterol Guidelines and Prevalent Use of Medication to Lower Lipid Levels in an Older US Cohort: The Atherosclerosis Risk in Communities Study Cohort. JAMA Intern Med 2014 Nov 17. [Epub ahead of print]
  8. Maddox TM, Borden WB, Tang F, et al. Implications of the 2013 ACC/AHA Cholesterol Guidelines for Adults in Contemporary Cardiovascular Practice: Insights From the NCDR PINNACLE Registry. J Am Coll Cardiol 2014;64:2183-92.
  9. Appelros P, Stegmayr B, Terént A. Sex differences in stroke epidemiology: a systematic review. Stroke 2009;40:1082-90.
  10. Tsai CF, Thomas B, Sudlow CL. Epidemiology of stroke and its subtypes in Chinese vs white populations: a systematic review. Neurology 2013;81:264-72.
  11. Blaha MJ, Blumenthal RS, Budoff MJ, Nasir K.  Understanding the utility of zero coronary calcium as a prognostic test: a Bayesian approach. Circ Cardiovasc Qual Outcomes 2011;4:253-6.
  12. Tota-Maharaj R, Blaha MJ, McEvoy JW, et al. Coronary artery calcium for the prediction of mortality in young adults and elderly adults. Eur Heart J. 2012 Dec;33(23):2955-62.
  13. Silverman MG, Blaha MJ, Krumholz HM, et al. Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis. Eur Heart J 2014;35:2232-41.
  14. IMPROVE-IT Trial: A Comparison of Ezetimibe/Simvastatin versus Simvastatin Monotherapy on Cardiovascular Outcomes After Acute Coronary Syndromes. Christopher P Cannon, On behalf of the IMPROVE IT Investigators. Presented at Late Breaking Trials, Scientific Sessions-American Heart Association, November 19, 2014.

Clinical Topics: Clinical Topic Collection: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: American Heart Association, Azetidines, Cholesterol, LDL, Coronary Vessels, Diabetes Mellitus, Drug Combinations, Health Personnel, Heart Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Nutrition Surveys, Registries, Risk Assessment, Simvastatin


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