ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study

Abstract

Aim: We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria.

Methods and results: We examined 44 889 individuals aged 40-75 recruited in 2003-09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (-35% for any ASCVD and -36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%.

Conclusions: The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit.

Keywords: Atherosclerosis; Guideline; Lipids; Lipoproteins; Myocardial infarction; Stroke.

Figure 1

Calibration comparing observed and predicted events in 40- to 75-year-old individuals in the Copenhagen General Population Study. US PCE performed well below 10% any atherosclerotic cardiovascular disease 10-year risk, with good calibration around the guideline-defined decision thresholds of 5% and 7.5% for statin therapy (left panel). In contrast, European SCORE overestimated risk across all deciles and categories of fatal atherosclerotic cardiovascular disease 10-year predicted risk, with substantial overestimation around both the high-risk (5%) and very-high-risk (10%) thresholds for statin therapy (right panel). Observed events were Kaplan–Meier adjusted. Error bars indicate 95% confidence interval. PCE,  pooled cohort equations; SCORE,  Systematic COronary Risk Evaluation.

Figure 2

Eligibility for statin therapy using ACC/AHA and ESC/EAS guidelines in individuals aged 40–75 years in the Copenhagen General Population Study. Proportion of individuals who qualified for primary prevention with statins based on Class I and IIa recommendations as shown in Table 1. A larger proportion of individuals qualified for statins with the ACC/AHA guidelines compared with the ESC/EAS guidelines. For conversion of cholesterol values in mmol/L to mg/dL, multiply by 38.6. ACC/AHA, American College of Cardiology/American Heart Association; ESC/EAS, European Society of Cardiology/European Atherosclerosis Society; PCE, pooled cohort equations; SCORE, Systematic COronary Risk Evaluation; LDL-C , Low-density lipoprotein cholesterol; TC ,  Total cholesterol.

Figure 3

Correlation between European SCORE fatal atherosclerotic cardiovascular disease 10-year risk and US PCE any atherosclerotic cardiovascular disease 10-year risk. Risk estimated by European SCORE and US PCE correlated strongly in the decision interval of interest in both men (A) and women (B). Analyses were by linear regression. The fitted regression lines include 95% confidence bands (too narrow to be seen). ASCVD, atherosclerotic cardiovascular disease; PCE, pooled cohort equations; SCORE, Systematic COronary Risk Evaluation.