Guidelines versus trial-evidence for statin use in primary prevention: The Copenhagen General Population Study

Martin Bødtker Mortensen,Børge Grønne Nordestgaard

doi:10.1016/j.atherosclerosis.2021.12.002

Martin Bødtker Mortensen, Børge Grønne Nordestgaard

Open Access

https://doi.org/10.1016/j.atherosclerosis.2021.12.002

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Abstract

Background and aimsGuideline-recommended use of risk calculators to select for statin therapy in primary prevention has never been tested in a randomized controlled trial (RCT). We determined the extent to which guideline-based statin recommendations from the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society(CCS), UK National Institute for Health and Care Excellence (NICE), and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) is supported by available evidence from RCTs. Methods79,171 individuals from the Copenhagen General Population Study who were free of ASCVD and statin use at baseline were included. RCT evidence supporting guideline-recommended statin allocation and the estimated number needed to treat (NNT) to prevent one ASCVD event were assessed. ResultsDuring 8.2 years of follow-up, 4031 ASCVD events occurred. Of individuals eligible for statin therapy with the ACC/AHA, CCS, NICE and ESC/EAS guidelines, 86%, 88%, 88% and 84% had direct RCT evidence of statin efficacy, respectively (guideline-positive&RCT-positive). This group represented 26–37% of all 79,171 individuals, while guideline-positive&RCT-negative individuals represented 5–7%, guideline-negative&RCT-positive individuals 28–39%, and guideline-negative&RCT-negative individuals represented 30–31%. The ASCVD events per 1000 person-years were 11.4–12.7 (guideline-positive&RCT-positive), 6.3–8.0 (guideline-positive&RCT-negative), 4.2–5.2 (guideline-negative&RCT-positive), and 2.3–2.5 (guideline-negative&RCT-negative), respectively, while the corresponding NNT to prevent one event in 10 years using high-intensity statin were 19–21, 30–32, 48–60, and 105–125, respectively. ConclusionsThe far majority of individuals eligible for guideline-recommended primary prevention with statins have direct RCT evidence supporting statin use. Allocating statins based on guideline-criteria is more efficient with lower NNT for preventing ASCVD events than allocating statin therapy based solely on RCT evidence.

Highlights

All major international guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD) with statin therapy share the principle of allocating treatment based on predicted absolute risk of developing ASCVD [1,2,3,4]
These results support the use of guideline recommendations, including risk calculators, for evidencebased allocation of primary prevention with statin therapy and they demonstrate that the evidence base for the beneficial effects of LDL-C lowering is overwhelming in the primary prevention setting
Our data raise an important new question: should the very large group of individuals with randomized controlled trial (RCT)-based evidence of statin efficacy but without a concomitant guideline recommendation be candidates for statin therapy? Our analyses show that such individuals generally had low event-rates compared to guideline-eligible individuals, implying that their short term (≈10 year) net benefit of statin therapy is relatively low

Summary

Introduction

All major international guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD) with statin therapy share the principle of allocating treatment based on predicted absolute risk of developing ASCVD [1,2,3,4] For this purpose, a specific guideline-recommended risk calculator is used to estimate 10-year risk of ASCVD in individuals free of known ASCVD at the time of risk assessment. We determined the extent to which guideline-based statin recommendations from the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society(CCS), UK National Institute for Health and Care Excellence (NICE), and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) is supported by available evidence from RCTs. Methods: 79,171 individuals from the Copenhagen General Population Study who were free of ASCVD and statin use at baseline were included. Allocating statins based on guideline-criteria is more efficient with lower NNT for preventing ASCVD events than allocating statin therapy based solely on RCT evidence

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