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

BACKGROUND AND AIMS: Guideline-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.

METHODS: 79,171 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.

RESULTS: During 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.

CONCLUSIONS: The 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.