BACKGROUND
In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) cholesterol treatment guidelines1 expanded primary prevention statin eligibility based on atherosclerotic cardiovascular risk score (ASCVD) compared with the 2002 Adult Treatment Panel III (ATP II) guidelines.1,2 Previous studies have examined recent trends in primary prevention statin use, but have not assessed the impact of guideline changes.3 We hypothesized greater increases in primary prevention statin use among adults newly recommended statins by the ACC/AHA guidelines.
OBJECTIVE
To describe trends in primary prevention statin use across indication categories and ASCVD risk scores.
METHODS
This was a repeated cross-sectional study examining statin use among non-pregnant adults aged 20 years or greater, without known ASCVD, and who provided fasting laboratory data, using National Health and Nutrition Examination Survey from 1999 to 2018. For adults who reported taking a statin, baseline (off-statin) cholesterol levels were estimated using a correction factor for each statin based on prior meta-analysis data.1 We defined adults as previously, newly, or continuously statin-eligible if they met criteria for statin use by only the 2002 ATP III guidelines, by only the 2013 ACC/AHA guidelines, or by both guidelines respectively. Adults who met multiple primary prevention indications by AHA/ACC guidelines were assigned by the highest criteria met, consistent with guideline hierarchy (LDL-C criteria > diabetes status > ASCVD risk).1 Survey weighting and multiple imputation for missing values were conducted per NHANES recommendations.4 Analyses were conducted using Stata v16.1.
FINDINGS
The study cohort included 21,961 adults, representing a weighted population that varied from 173.9 million (95% CI, 152.3 – 195.5) in 1999/2000 to 215.5 million (95% CI, 192.3 – 238.7) in 2017/2018 of whom 35.6% (95% CI, 34.5% - 36.8%) had an indication for primary prevention statin use (Table 1). From 1999–2000 to 2013–2014, the proportion of guideline-eligible adults who reported taking statins increased from 11.6% (95% CI, 7.7% - 15.6%) to 33.6% (95% CI, 27.5% - 39.6%), a 22.0% point increase (95% CI, 14.7% - 29.2%). From 2013–2014 to 2017–2018 there was no clear change in statin use (−1.2% point decrease; 95% CI, −8.6% - 6.3%) (Figure 1A).
Table 1.
Cohort Characteristics
| Overall* | Indication for Primary Prevention Statin | |
|---|---|---|
| Unweighted N | 21,691 | 9,895 |
| Weighted N, billions (95% CI) | 1.96 (1.89 to 2.03) | 0.70 (0.66 to 0.73) |
| % of Overall, (95% CI) | 100 | 35.6 (34.5 to 36.8) |
|
| ||
| Demographics, % (95% CI) | ||
| Age category, y | ||
| 20–39 | 40.0 (38.9 to 41.2) | 2.2 (1.7 to 2.6) |
| 40–59 | 38.8 (37.8 to 39.8) | 43.6 (42.1 to 45.1) |
| 60–74 | 15.8 (15.0 to 16.7) | 39.4 (37.9 to 40.9) |
| ≥ 75 | 5.3 (5.0 to 5.7) | 14.9 (13.9 to 15.8) |
| Female | 51.8 (51.1 to 52.5) | 47.8 (46.4 to 49.1) |
| Race/ethnicity | ||
| Asian | 2.5 (2.1 to 2.9) | 2.3 (1.9 to 2.7) |
| Black | 12.0 (10.0 to 12.2) | 11.6 (10.2 to 13.0) |
| Hispanic | 14.2 (12.6 to 15.8) | 10.6 (9.0 to 12.1) |
| Other/Multi-Racial | 4.5 (3.9 to 5.0) | 3.7 (3.1 to 4.3) |
| White | 67.8 (65.6 to 69.9) | 71.8 (69.5 to 74.2) |
| Education | ||
| <12th Grade | 16.6 (15.6 to 17.6) | 19.9 (18.6 to 21.3) |
| High School Graduate | 23.9 (22.8 to 25.0) | 26.6 (25.0 to 28.2) |
| Some College | 31.1 (30.0 to 31.1) | 28.6 (28.0 to 30.1) |
| College Graduate | 28.3 (26.7 to 30.0) | 24.8 (23.0 to 26.6) |
| Health insurance | ||
| Commercial | 51.1 (49.8 to 52.4) | 37.9 (36.3 to 40.0) |
| Medicaid | 5.7 (5.1 to 6.2) | 5.4 (4.7 to 6.2) |
| Medicare | 17.1 (16.3 to 17.9) | 35.6 (34.2 to 37.0) |
| Other | 7.5 (6.9 to 8.1) | 9.8 (8.7 to 10.9) |
| Uninsured | 18.7 (17.6 to 19.7) | 11.3 (10.3 to 12.3) |
| Received healthcare in the past year | 81.0 (80.1 to 81.8) | 89.0 (88.1 to 90.0) |
| Usual source of healthcare | 82.6 (81.8 to 83.3) | 89.2 (88.2 to 90.0) |
| Body mass index, kg/m2 | ||
| <18.5 | 1.8 (1.5 to 2.0) | 1.0 (0.7 to 1.3) |
| 18.5–24.9 | 30.1 (29.6 to 31.7) | 22.9 (21.6 to 24.2) |
| 25–29.9 | 33.0 (32.1 to 33.9) | 35.5 (34.1 to 37.0) |
| ≥ 30 | 34.6 (33.5 to 35.7) | 40.6 (39.1 to 42.0) |
| Smoking in past year | 21.1 (20.0 to 22.2) | 22.2 (20.8 to 23.6) |
| Indication for Statin for Primary Prevention, % (95% CI) *† | ||
| Any Indication | 35.6 (34.4 to 36.8) | 100 |
| LDL≥190 mg/dL | 3.6 (3.3 to 4.0) | 10.2 (9.2 to 11.1) |
| Diabetes | 9.0 (8.5 to 9.5) | 25.3 (24.0 to 26.6) |
| ASCVD Risk ≥ 20% | 7.8 (7.3 to 8.3) | 22.0 (20.7 to 23.3) |
| ASCVD Risk 7.5% to 19.9% | 9.9 (9.3 to 10.6) | 27.9 (26.5 to 29.3) |
| ASCVD Risk 5.0% to 7.5% | 5.2 (4.8 to 5.7) | 14.7 (13.9 to 15.8) |
Note: Missing values were imputed using multiple imputation, including: smoking status (N=24), body mass index (n=344), received healthcare in the past year (N=13).
Overall cohort consists of participants meeting all eligibility criteria and without a secondary prevention indication for statin use.
Baseline ASCVD risk scores for adults taking statins were calculated using a correction factor for each statin based on prior meta-analysis data (Naci H, Brugts JJ, Fleurence R, Ades AE. Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev Cardiol. 2013;20(4):658–670. doi:10.1177/2047487313483600
Individual indication categories were mutually exclusive. Adults who met multiple primary prevention indications by AHA/ACC guidelines were assigned by the highest criteria met, consistent with guideline hierarchy (LDL-C criteria > diabetes status > ASCVD risk).1
Figure 1:
Trends in proportion of patients eligible for primary prevention statin who reported statin use
Footnote: Vertical black line indicates release of 2013 ACC/AHA guideline. Panels A, C, and D use ACC/AHA guideline criteria for all years to determine the denominator of statin eligibility. Panel D includes patients whose only indication is ASCVD risk and does not include patients with diabetes or severely elevated LDL cholesterol which are depicted in Panel C.
* Overall trend from 1999/2000 to 2017/2018 showed 20.8% point increase in statin use (95% CI: 14.9% - 26.7%). From 1999/2000 to 2013/2014 there was a 22% point increase (95% CI: 14.7% - 29.2%). From 2013/2014 to 2017/2018 there was a no clear change (−1.2% point decrease; 95% CI: −8.6% - 6.3%).
† 2002 ATP III Guidelines2; 2013 ACC/AHA guidelines1. For the overall study period, from 1999/2000 to 2017/2018, there was a 6.8% point increase in statin use (95% CI: −17.9 – 31.4) for adults recommended statins by ATP III only, a 13.6% point increase (95% CI: 2.7% - 24.5%) for adults recommended statins by AHA only, and a 28.4% point increase (95% CI: 20.2% - 36.6%) for adults recommended statins by both guidelines (continuously recommended). From 1999/2000 to 2013/2014 there was no clear change for adults recommended statins by ATP III only (7.1% point increase; 95% CI: −17.7% - 31.9%), a 15.6% point increase (95% CI: 4.3% - 27.0%) for adults recommended statins by AHA only, and a 27.9% point increase (95% CI: 19.6% - 36.2%) for adults recommended statins by both guidelines. From 2013/2014 to 2017/2018 there was no clear change in statin use for any group: −0.3% point decrease (95% CI: −25.9% - 25.3%) for adults recommended statins by ATP III only; −2.1% point decrease (95% CI: −15.1% - 11.0%) for adults recommended statins by AHA only, and 0.5% point increase (95% CI: −7.9% - 8.9%) for adults recommended statins by both guidelines.
‡ For the overall study period, from 1999/2000 to 2017/2018, there was a 10.3% point increase in statin use (95% CI: −5.6% - 26.2%) for adults with an indication based on LDL ≥ 190 mg/dl, a 37.9% point increase (95% CI: 24.3% - 51.6%) for adults with an indication based on diabetes, and a 14.7% point increase (95% CI: 8.2% - 21.2%) for adults with an indication based on ASCVD risk >5.0%. From 1999/2000 to 2013/2014 there was no clear change for adults with an indication based on LDL ≥ 190 mg/dl (14.0% point increase; 95% CI: −3.2% - 31.2%), a 31.1% point increase (95% CI 21.0% - 41.2%) for adults with an indication based on diabetes, and a 19.3% point increase (95% CI: 9.9% - 28.8%) for adults with an indication based on ASCVD risk >5.0%. From 2013/2014 to 2017/2018 there was no clear change in statin use for any group: a 3.7% point decrease (95% CI: −21.8% - 14.4%) for adults with an indication based on LDL ≥ 190 mg/dl; 6.8% point increase (95% CI: −7.3% - 21.0%) for adults with an indication based on diabetes, and 4.6% point decrease (95% CI: −13.3% - 4.2%) for adults with an indication based on ASCVD risk >5.0%.
§ For the overall study period, from 1999/2000 to 2017/2018, there was no clear change for adults with ASCVD risk 5.0–7.5% (9.6% point increase; 95% CI: −4.4% - 23.6%) for adults with ASCVD risk 7.5–19.9% (11.2% point increase; 95% CI: −0.2% - 22.6%), and a 22.7% point increase (95% CI: 10.2% - 35.2%) for adults with ASCVD risk >20.0%. From 1999/2000 to 2013/2014 there was no clear change for adults with ASCVD risk 5.0–7.5% (12.0% point increase; 95% CI: −0.7% - 24.7%), a 20.6% point increase for adults with ASCVD risk 7.5–19.9% (95% CI: 8.8% - 32.5%), and a 23.1% point increase (95% CI: 11.4% - 34.8%) for adults with ASCVD risk >20.0%. From 2013/2014 to 2017/2018 there was no clear change in statin use for any ASCVD group: 2.4% point decrease (95% CI: −19.2% - 14.5%) for adults with ASCVD risk 5.0–7.5%; 9.4% point decrease (95% CI: −21.9% - 3.1%) for adults with ASCVD risk 7.5–19.9%, and 0.4% point decrease (95% CI: −13.2% - 12.3%) for adults with ASCVD risk >20.0%.
For adults newly recommended statins by the 2013 ACC/AHA guidelines, the proportion using statins did not change between 2013–2014 and 2017–2018 (−2.1% point decrease; 95% CI, −15.1% - 11%) (Figure 1B). Adults with diabetes had a 31.1% point increase (95% CI, 21.0% - 41.2% ) in proportion using statins from 1999–2000 to 2013–2014 but no change from 2013–2014 to 2017–2018 (6.8% change; 95% CI, −7.3% - 21.0%) (Figure 1C). Adults with ASCVD risk > 20% had a clear increase in statin use from 1999–2000 to 2013–2014 (23.1% point increase; 95% CI, 11.4%–34.8%), but not from 2013–2014 to 2017–2018 (−0.4% point decrease; 95% CI, −13.2% - 12.3%). Among adults with an ASCVD risk-based indication, between the three group of ASCVD risk, patterns of statin use were similar over time (Figure 1D)
DISCUSSION
Although overall primary prevention statin use has increased over time, it has plateaued at only 35% since publication of the 2013 ACC/AHA guidelines. Furthermore, the majority of adults with guideline recommendations for primary prevention statins are not taking them, including those with diabetes or LDL cholesterol ≥ 190 mg/dl, indicating that novel efforts, informed by implementation science and targeting patients with the greatest risk, are urgently needed.
While the ACC/AHA guidelines expanded indications for primary prevention, they also increased decision-making complexity, requiring new multi-step risk calculation. Our findings demonstrated a lower rate of statin use among patients meeting criteria based on ASCVD risk compared to those with easily identifiable indications such as diabetes or LDL ≥ 190 mg/dl. Many clinicians do not routinely use cardiovascular risk calculators, due to lack of time, availability of inputs, or lack of buy-in.5 Electronic health record tools that calculate ASCVD risk show promise, but are not routinely implemented, and do not address other barriers such as competing patient priorities and limited time for shared-decision-making.
Study limitations include lack of data on whether adults had previously been offered and declined statin therapy and estimation of baseline ASCVD risk scores to account for changes in lipid concentrations for patients taking statins, which may impact the ASCVD risk classification of patients receiving statins.
ACKNOWLEDGEMENTS
Funding/Support:
Dr. Anderson was supported by grant K76AG074878 from the National Institute on Aging. Dr. Mukamal was supported by a grant K24AG065525 from the National Institute on Aging
Role of the Funder/Sponsor:
The National Institute on Aging had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Footnotes
Conflict of Interest Disclosures: Dr. Sussman reports receiving grants from the NIH and US Department of Veterans Affairs outside of the submitted work. Dr. Anderson reports receiving grants from the American Heart Association, American College of Cardiology, Boston OAIC Pepper Center, and US Deprescribing Research Network outside the submitted work.
Disclaimer: The research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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