Summary
The US Preventive Services Task Force (USPSTF) published a recommendation on statin use for primary prevention in 2016 [1]. Now the task force has commissioned a new review of the evidence on the benefits and harms of statins as the basis for an update of the 2016 guidelines [2]. There were 26 studies included in the review, 23 randomised trials and three observational studies. Since the 2016 review, there was only one new trial but separate primary prevention data had become available from some other studies. The main finding was that there is moderate certainty that statin use offers moderate net benefit (in terms of reduced risk of cardiovascular disease (CVD) events and all-cause mortality) for adults aged 40-75 years with no history of cardiovascular disease but have at least one CVD risk factor and an estimated 10-year risk of a CVD event of at least 10% [3]. This recommendation does not apply to people with a LDL cholesterol level above 4.92 mmol/L, those with familial hypercholesterolaemia or adults aged over 75 years. The USPSTF also recommends that statins could be considered for adults aged 40-75 years with no history of CVD and at least one CVD risk factor and an estimated 10-year risk of a CVD event of between 7.5 and 10%.
Commentary
The main message of the 2022 USPSTF recommendation about the use of statins for primary prevention is essentially unchanged from that in 2016. However, the estimated benefits of statin therapy had been “slightly attenuated”. This was because with the inclusion of the new data, the overall estimated reduction in the risk of CVD mortality was smaller and no longer statistically significant. However, the main recommendation for intervention remains for those aged 40-75 with at least one CVD risk factor and an estimated risk of a cardiovascular event within the next 10 years of at least 10%. It is understandable that busy clinicians would follow treatment recommendations coming from a body such as the USPSTF, however a number of the commentaries published about the new recommendations are worthy of consideration [4]. One editorial questioned the premise of primary prevention with statins given that the new systematic review does not show a statistically significant reduced risk of cardiovascular mortality [5]. The authors also questioned the use of the pooled cohort equations used to estimate 10-year risk of an event given that the data on which they are based are old (1960’s to 1980’s), mainly included men, and do not reflect recent improvements in rates of CVD events. The same authors emphasised that 19 of the trials included in the USPSTF systematic review were industry-sponsored.
Another commentary also addressed the issue of 10-year risk categories [6]. As individuals with the highest underlying absolute risk stand to gain the most from an intervention, it is understandable that the strongest recommendation for the intervention is for individuals at highest risk of a cardiovascular event. However, the authors argue that the use of a risk assessment based on the likelihood of an event within 10 years may disadvantage some groups. They use as an example a woman at midlife with an elevated LDL cholesterol level who may not meet the 10-year risk criterion, yet would likely have a 50% lifetime risk of a cardiovascular event. Waiting until that woman reached the 10-year risk threshold does not seem to fit with the concept of primary prevention.
A comparison of the USPSTF recommendations with guidelines from other bodies (the American Heart Association and the American College of Cardiology) highlighted that those bodies include other considerations along with the 10-year risk of an event, including risk-enhancing factors, which, importantly for women, includes premature menopause [7].
Beyond the argument about the appropriateness of the approach to assessing cardiovascular risk, it is already known that women eligible for statin therapy according to guidelines are less likely to use statin therapy than men which appears to be combination of both fewer women being prescribed therapy as well as women being more likely to refuse or discontinue lipid therapy [8].
In 2019 the Lancet established a commission on women and cardiovascular disease [9]. This was done in the context of CVD being the leading cause of death in women although women were less likely than men to be diagnosed early or receive timely intervention. The commission report in 2021 [10] emphasised that the approach to CVD in women is still hampered by inadequate understanding of CVD risk in women and its assessment.
Clinicians involved in the management of women’s health have an opportunity to “assess and empower women to recognise CVD risk” [10] as well as to advocate for further research into CVD risk assessment that includes sex-specific considerations.
Robin Bell, MD
Deputy Director of the Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
References
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997-2007.
https://pubmed.ncbi.nlm.nih.gov/27838723/ - Chou R, Cantor A, Dana T, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;328(8):754-771.
https://pubmed.ncbi.nlm.nih.gov/35997724/ - US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;328(8):746-753.
https://pubmed.ncbi.nlm.nih.gov/35997723/ - Stiles S. ‘Conservative’ USPSTF Primary Prevention Statin Guidance Finalized: medscape; 2022.
Available at https://www.medscape.com/viewarticle/979686#vp_3. - Habib AR, Katz MH, Redberg RF. Statins for Primary Cardiovascular Disease Prevention: Time to Curb Our Enthusiasm. JAMA Intern Med. 2022;182(10):1021-1024.
https://pubmed.ncbi.nlm.nih.gov/35997985/ - Navar AM, Peterson ED. Statin Recommendations for Primary Prevention: More of the Same or Time for a Change? JAMA. 2022;328(8):716-718.
https://pubmed.ncbi.nlm.nih.gov/35997751/ - Stone NJ, Greenland P, Grundy SM. Statin Usage in Primary Prevention-Comparing the USPSTF Recommendations With the AHA/ACC/Multisociety Guidelines. JAMA Cardiol. 2022 Aug 23. doi: 10.1001/jamacardio.2022.2851.
https://pubmed.ncbi.nlm.nih.gov/35998005/ - Nanna MG, Wang TY, Xiang Q, et al. Sex Differences in the Use of Statins in Community Practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562.
https://pubmed.ncbi.nlm.nih.gov/31416347/ - Mehran R, Vogel B, Ortega R, Cooney R, Horton R. The Lancet Commission on women and cardiovascular disease: time for a shift in women’s health. Lancet. 2019;393(10175):967-968.
https://pubmed.ncbi.nlm.nih.gov/30765122/ - Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet. 2021;397(10292):2385-2438.
https://pubmed.ncbi.nlm.nih.gov/34010613/
If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui, at peter.chedraui@cu.ucsg.edu.ec.
