High Quality Statin Trials Support the 2013 ACC/AHA Cholesterol Guidelines After HOPE-3: The Multi-Ethnic Study of Atherosclerosis

Abstract

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline on cholesterol treatment to prevent atherosclerotic cardiovascular disease (ASCVD) has been criticized for lowering the risk thresholds for primary prevention with statin therapy. Although the ≥ 7.5% (class I) and ≥ 5% (class IIa) 10-year ASCVD risk thresholds were identified as new indications for treatment by extrapolating results obtained in randomized controlled trials (RCT) of statin therapy, results from population-based European cohorts indicate that >30% of individuals eligible for statin therapy by class I recommendations do not have RCT data supporting statin efficacy. Further, when the US Preventive Services Task Force published their recommendations (based on review of trial evidence), they restricted the indication for statin therapy compared with the ACC/AHA guideline by recommending a higher treatment threshold (10%) combined with ≥1 ASCVD risk factor. However, the evidence base for statins in primary prevention grew substantially in 2016 with publication of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial that enrolled intermediate-risk persons for whom a clear indication for statin therapy was still lacking. The implications of HOPE-3 for the evidence base supporting ACC/AHA risk-based statin allocation remain unknown. Therefore, using MESA (Multiethnic Study of Atherosclerosis, www.mesa-nhlbi.org) - a population-based US cohort - we assessed the extent to which the ACC/AHA recommendations for statin therapy are supported by currently available high-quality RCT evidence: WOSCOPS, AFCAPS/TexCAPS, ASCOT-LLA, CARDS, MEGA, JUPITER and HOPE-3 (ref. 2 and 4 for details). Given the controversy that exists in whom to treat with statins in primary prevention, such information may provide important insights for clinical practice and future updates of guidelines and recommendations.