With inclusion of the HOPE-3 (Heart Outcomes Prevention Evaluation-3) trial, evidence from seven high-quality randomized controlled trials (RCTs) now supports statin efficacy for nearly all individuals qualifying for primary prevention statin therapy with an American College of Cardiology/American Heart Association (ACC/AHA) Class I recommendation.

The 2013 ACC/AHA guidelines on treatment of blood cholesterol to reduce atherosclerotic risk in adults have been previously criticized for reducing the risk threshold for statin treatment in primary prevention. Prior estimates suggested that >30% of individuals eligible for statin therapy by ACC/AHA Class I guidelines did not have RCT data to support the recommendation. The guidelines recommend that statin use be considered for people aged 40-75 with low-density lipoprotein cholesterol (LDL-C) of 70-189 and 10-year atherosclerotic cardiovascular disease (ASCVD) risk of >7.5% (Class I) or 10-year ASCVD risk of 5-7.5% (Class IIa), in addition to patients with known ASCVD, LDL-C ≥ 190, or diabetics aged 40-75. However, the HOPE-3 trial (published May 2016) provided solid evidence supporting use of statin therapy in intermediate-risk people. These findings and the 2013 ACC/AHA guidelines for cholesterol treatment can provide a starting point for physician-patient discussions regarding initiation of statin treatment.

The following are key points to remember from this MESA (Multi-Ethnic Study of Atherosclerosis) cohort analysis:

1. The researchers evaluated the MESA cohort to analyze the extent to which evidence from seven high-quality RCTs now support the 2013 ACC/AHA recommendations for statin therapy. The MESA cohort, from 6 centers across the United States, included 4,967 people aged 45-75 who were free of known ASCVD or lipid-lowering medications at baseline.
2. In this analysis, 94% of people with 10-year ASCVD risk of >7.5% (Class I ACC/AHA recommendation) had an indication for statin therapy supported by RCT evidence. Of people with a 10-year ASCVD risk of 5-7.5% (Class IIa ACC/AHA recommendation), 78% had an indication supported by RCT evidence.
3. The seven high-quality RCTs identified were WOSCOPS (The West of Scotland Coronary Prevention Study), AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study), ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm), CARDS (Collaborative Atorvastatin Diabetes Study), MEGA (Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese), JUPITER (Justification for the Use of Statins in prevention: An Intervention Trial Evaluating Rosuvastatin), and HOPE-3.
4. The HOPE-3 trial provided much of the previously missing RCT supporting evidence. It provided supportive RCT evidence in 21% of people with 10-year ASCVD risk of >7.5% (Class I ACC/AHA indication). Prior to HOPE-3, only 73% of people with 10-year risk of >7.5% had RCT evidence to support statin therapy.
5. The ASCVD event rate (myocardial infarction, resuscitated cardiac arrest, congenital heart disease death, or stroke) over a median 10-year follow-up period in the MESA participants was higher in individuals with an ACC/AHA Class I indication than in individuals with a trial-based indication.

Keywords: Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cholesterol, Atherosclerosis, Coronary Artery Disease, Primary Prevention, Randomized Controlled Trial

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