Determining Statin Eligibility to Prevent Cardiovascular Disease

Study Questions:

Current guidelines recommend statins in primary prevention of cardiovascular disease when the low-density lipoprotein cholesterol (LDL-C) is ≥190 mg/dl and when 10-year cardiovascular risk is at least 7.5% and LDL-C is 70-189 mg/dl. What is the comparative relative benefit of statin therapy based on available evidence from five primary prevention randomized clinical trials?


A total of 2,134 participants represented 71.8 million American residents potentially eligible for statins in primary prevention from the National Health and Nutrition Examination Survey for years 2005–2010. Statin eligibilities for benefit were compared between two separate approaches: a 10-year risk-based approach and an individualized benefit approach (i.e., based on predicted absolute risk reduction over 10 years [ARR10] ≥2.3% from randomized clinical trial data).


A risk-based approach led to the eligibility of 15.0 million Americans, whereas a benefit-based approach identified 24.6 million. The corresponding numbers needed to treat over 10 years were 21 and 25. The benefit-based approach identified 9.5 million lower-risk (<7.5% 10-year risk) Americans not currently eligible for statin treatment, who had the same or greater expected benefit from statins (≥2.3% ARR10) as higher-risk individuals. This lower-risk/acceptable-benefit group includes younger individuals (mean age 55.2 years vs. 62.5 years; p < 0.001 for benefit-based vs. risk-based) with higher LDL-C (140 mg/dl vs.133 mg/dl; p = 0.01). Statin treatment among this group would be expected to prevent an additional 266,508 cardiovascular events over 10 years.


An individualized statin benefit approach can identify lower-risk individuals who have equal or greater expected benefit from statins in primary prevention than higher-risk individuals. This may help develop guideline recommendations that better identify individuals who meaningfully benefit from statin therapy.


One of the concerns with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines has been the heavy weighting of age such that nearly all men >65 and women >70 years old have >7.5% 10-year risk and an LDL-C ≥70 mg/dl. Middle-aged men and women with a high LDL-C do not warrant statins by 10-year risk, but have a relatively high life-long risk of cardiovascular events and for whom the absolute reduction in cardiovascular risk is similar to those at higher risk. Over time, we will also learn to further personalize decisions with coronary artery calcium scores, lipoprotein (a), and high-sensitivity C-reactive protein, and novel biomarkers of risk for cardiovascular events.

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

Keywords: Cardiovascular Diseases, Cholesterol, LDL, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Metabolic Syndrome X, Primary Prevention, Risk Assessment, Risk Factors

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