More individuals eligible for primary prevention with statins in the 2019 ESC/EAS guidelines
2019 vs. 2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular disease
Introduction and methods
The 2016 ESC/EAS guidelines for management of dyslipidemia recommend the same treatment criteria as in previous guidelines, while other guidelines from the USA, Canada and the UK (ACC/AHA, USPSTF, CCS, NICE) recommend considerably lower treatment threshold for statin therapy. In addition, the 2016 ESC/EAS guidelines recommend class I/A statin therapy to individuals aged 40-65 years, while other guidelines advise statin therapy to those aged 40-75 years [1-5]. While these other guidelines targeted statin therapy to 31-44% of adults, the 2016 ESC/EAS guidelines only targeted 15% of adults. This leads to an estimated percentage of ASCVD events that could have been prevented by statin therapy for 10 years of 34% for ACC/AHA, 27% for USPSTF, 34% for CCS, and 32% for NICE compared to only 13% for ESC/EAS .
The 2019 ESC/EAS guidelines for primary prevention with statin use contain several important changes: 1) an updated Systemic Coronary Risk Evaluation (SCORE) risk assessment chart, also applicable to people older than 65, 2) eligibility was expanded with lower untreated LDL-cholesterol concentration eligible for class I/A statin therapy, and 3) class I/A recommendations for statin treatment is also provided for individuals aged 66-75 .
The current study compared the 2019 and 2016 guidelines for the management of dyslipidemias in regard to statin eligibility and potential impact on prevention in ASCVD in the general population using data from the Copenhagen General Population Study (CGPS).
The CGPS is an ongoing prospective cohort study of the Danish population that reflects the white general population in Copenhagen and surrounding area. For this study, individuals (n=45,750) aged 40-75 who enrolled between 2003 and 2009 and were free of ASCVD and statin use at baseline were included. Mean follow-up was 9.2 years. Age, sex, smoking, total cholesterol, and SBP were used to estimate the risk for ASCVD with the SCORE charts. The clinical performance of the 2019 and 2016 guidelines for ASCVD (fatal and non-fatal MI, stroke, and coronary death) were compared. The proportion of people eligible for statin treatment were calculated using the class I/A recommendations for primary prevention with statins for both guidelines and this study assessed which 2019 guideline change contributed to the increased eligibility for statin therapy. Also, sensitivity, specificity, positive predictive value and negative predictive value of the two guidelines were assessed. Lastly, the potential impact for ASCVD prevention over 10 years through full implementation of the guidelines was estimated.
- The proportion of individuals eligible for statin therapy at baseline according to Class I/A recommendation were 32.3% (95% CI:31.8-32.7%) according to the 2019 guidelines compared to 15.4% (95% CI:15.1-15.7%) using the 2016 guidelines. 17% Of individuals were eligible for statin treatment according to the new 2019 guidelines, but not with the guidelines from 2016. Alternatively, <1% of people who were eligible for statins using the 2016 guidelines, were not statin eligible with the new 2019 guidelines.
- When stratified by 5 year-age groups, there were more individuals in all age groups who were eligible for statin treatment with the 2019 guidelines, compared to the 2016 guidelines. In men and woman aged 66-75, statin eligibility was a lot higher using the 2019 guidelines.
- The cause of increase in eligibility for statin therapy using the 2019 guidelines was in 33.2% of individuals due to lowered LDL-c level threshold for statin therapy, in 49.4% due to the inclusion of the older age range, in 14.7% a combination of both LDL-c threshold lowering and recommendations for older age range, and in 2.8% due to the updated SCORE risk calculator.
- The lower LDL-c threshold for statin use in the 2019 guidelines, resulted in increased statin eligibility for individuals among all SCORE risk groups: 1153 people with SCORE 10-year fatal ASCVD risk <5%, 2278 people with SCORE 10-year fatal ASCVD risk ≥5% to <10%, and 337 people with SCORE 10-year fatal ASCVD risk ≥10% were captured additionally.
- The clinical usefulness and impact on ASCVD prevention of the LDL-c treatment threshold defined in the guidelines depends to the ability of this threshold to correctly assign statins to people who develop ASCVD in the future (sensitivity) and not to those who will not develop future ASCVD events (specificity). When comparing the 2019 guideline with the ones from 2016, there was an increase in sensitivity (56.5% in 2019 vs. 24.4% in 2016, P<0.0001) as well as specificity (85.3% in 2019 vs. 69.6% in 2016, P<0.0001). The positive and negative predictive values were similar between the two guidelines.
- When guidelines were fully implemented, the estimated percentages of ASCVD events that could have been prevented by high-intensity statins for 10 years were 25% using the 2019 guidelines and 11% with the 2016 guidelines. Using moderate-intensity statins, the ASCVD prevention in individuals would be 17% with the 2019 guidelines and 8 % using the 2016 guidelines.
- Number needed to treat (NNT) to prevent an ASCVD event were comparable within all age risk groups between the two guidelines.
Lower LDL-c threshold levels and class I/A recommendations for primary prevention with statin therapy to individuals aged 66-75 in the new 2019 ESC/EAS guidelines increased the number of individuals eligible for statin therapy and improved the potential impact for ASCVD prevention.