Lost opportunities for prevention if clinicians adopt USPSTF statin recommendations
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The U.S. Preventive Services Task Force in August published a statement regarding the initiation of statin therapy for the primary prevention of atherosclerotic CVD.
The USPSTF statement takes a much more conservative position on initiating statin therapy compared with the 2018 American Heart Association/American College of Cardiology/Multisociety Guideline on the Management of Blood Cholesterol. The latter emphasizes the importance of a patient-clinician discussion regarding the potential net benefit of statin therapy in addition to sustained lifestyle modifications. The differences between the documents are shown in the Table.
**As defined by 2022 USPSTF guidelines, this includes dyslipidemia, diabetes, hypertension and smoking.
According to the AHA/ACC/Multisociety guideline, the decision to initiate statin therapy should include assessment of patient-specific ASCVD risk factors as well as discussions of the ASCVD risk reduction seen in randomized controlled trials of statin therapy, rate of perceived adverse events of statin therapy, uncommon drug interactions with statins except for those with complicated drug regimens such as those on transplant or HIV medications, and patient preferences and values. The goal is to facilitate informed decision-making regarding statin therapy and to assess patient willingness to take a long-term medication to reduce ASCVD risk. Once patients are initiated on statin therapy, periodic blood tests are necessary to confirm adequate LDL reduction and patient adherence to the medication.
The AHA/ACC/Multisociety guideline concludes that statin therapy is a safe, low-cost and high-value intervention for ASCVD risk reduction that has shown consistent benefit for diverse patient populations.
The USPSTF recommendation excludes many individuals who would otherwise likely benefit from a statin by concluding that statin therapy has moderate net benefit in those with at least 10% 10-year ASCVD risk and small net benefit in those with 7.5% to 10% 10-year ASCVD risk. Approximately 16 million fewer adults from 2017 to 2020 would have been eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared with the 2018 AHA/ACC/Multisociety guideline. These discrepancies in clinical practice recommendations have serious implications for efforts at ASCVD risk reduction and can be challenging for health care providers to navigate.
The USPSTF recommendation relies heavily on the pooled cohort equation (PCE) risk estimator for 10-year ASCVD risk to guide clinical decision-making as opposed to encouraging a comprehensive approach that incorporates ASCVD risk-enhancing factors. The PCE risk estimator reports 10-year ASCVD risk based on age, sex, race (white, African American or other), systolic and diastolic BP, total cholesterol, HDL, LDL, presence of diabetes, smoking history and antihypertensive treatment.
Consideration of risk-enhancing factors should be routine
The PCE risk estimator does not include other important risk-enhancing factors such as family history of premature ASCVD (men younger than 55 years, women younger than 65 years); primary hypercholesterolemia with LDL consistently 160 mg/dL to 189 mg/dL or non-HDL 190 mg/dL to 219 mg/dL; persistent nonfasting hypertriglyceridemia ( 175 mg/dL); elevated high sensitivity C-reactive protein ( 2 mg/L); elevated lipoprotein(a) ( 30 mg/dL or 125 nmol/L); elevated apolipoprotein B ( 130 mg/dL); ankle-brachial index < 0.9; metabolic syndrome; chronic kidney disease; pregnancy-associated conditions such as preeclampsia that increase later CV risk and history of premature menopause (before age 40 years); chronic inflammatory disease processes such as rheumatoid arthritis, advanced psoriasis, HIV/AIDS and systemic lupus erythematosus; and higher-risk race/ethnicities such as South Asian ancestry.
Consequently, the actual ASCVD risk in these patient subgroups may be significantly underestimated by the risk calculator, resulting in ineligibility for statin therapy under the current USPSTF recommendation. The PCE estimator also risk-stratifies individuals as having a low (< 5%), borderline (5% to < 7.5%), intermediate ( 7.5% to < 20%) or high ( 20%) 10-year ASCVD risk. The USPSTF only recommends statin therapy for individuals who are estimated to be at intermediate or high risk for ASCVD, but clinicians often have patients with borderline 10-year ASCVD risk and multiple risk-enhancing factors who develop premature CAD and acute ischemic events.
Age is the dominant factor in the PCE risk estimator, and it is difficult for men younger than 55 years and women younger than 65 years to reach the 10-year ASCVD risk threshold of 10% as recommended by the USPSTF if they are nonsmokers and do not have diabetes. Even a PCE risk threshold of 7.5% has a fairly low sensitivity for capturing the true ASCVD risk in younger population. In patients younger than 40 years with multiple risk-enhancing ASCVD risk factors and persistently high LDL after a 6-month trial of aggressive lifestyle modifications, it would be beneficial to strongly consider initiation of statin therapy, as it has longitudinal benefit in slowing the progression of atherosclerosis and helping to stabilize more vulnerable plaques.
In these younger patients, it would also be meaningful to consider their 30-year or lifetime ASCVD risk when discussing benefits of initiating statin therapy. Lastly, the 2018 AHA/ACC/Multisociety guidelines make an important point that, in some patient populations, the calculation of an ASCVD score is not necessary for initiating statin therapy, as in the case of individuals aged 40 years or older with diabetes, or in the case of marked hypercholesterolemia (LDL > 190 mg/dL). These individuals are inherently at higher ASCVD risk than the general population.
Selective use of coronary artery calcium scoring as an option
Coronary artery calcium scoring can help guide clinical decision-making on statin therapy, and this has been highlighted in the 2018 AHA/ACC/Multisociety cholesterol guidelines. For individuals with borderline (5% to < 7.5%) or intermediate ( 7.5% to < 20%) 10-year ASCVD risk in whom there is uncertainty regarding the decision to initiate statins, CAC scoring can help with further risk stratification. If a patient with at least a 5% 10-year ASCVD risk and hyperlipidemia has tried to make sustained lifestyle improvements over 6 months, CAC scoring can be a very useful way to decide if statin therapy would be beneficial.
The CAC score is a more accurate measure of ASCVD risk compared with the PCE estimator, as it provides personalized risk assessment for adults as opposed to reporting average population-based risk. Furthermore, the presence of moderate CAC is correlated more strongly with ASCVD events than the PCE or other risk estimators. Data from the MESA cohort indicate that a CAC score of at least 100 Agatston units or at least 75th percentile for age, sex and race is generally associated with a 10-year ASCVD risk of at least 7.5%, which is the eligibility criteria for moderate-intensity statin therapy under the 2018 AHA/ACC/Multisociety cholesterol guideline.
Conversely, a CAC score of zero has strong negative predictive value and correlates with a low 10-year ASCVD risk (< 5%), and these individuals may not derive significant benefit from statin therapy over the next 10 years. Notably, Jaideep Patel, MD, and colleagues explored the correlation between multiple ASCVD risk-enhancing factors and CAC burden. Approximately 40% of the MESA participants with three or more risk-enhancing factors had no CAC, and their estimated 10-year ASCVD risk was relatively low at 5%. Nevertheless, the presence of multiple risk-enhancing factors is likely associated with increased 15-to-20-year risk, and these patients should engage in more intensive lifestyle modifications.
The USPSTF maintains that CAC scoring cannot be endorsed since there is no randomized prospective trial demonstrating that knowledge of the score improves clinical outcomes. However, that can be said for the PCE risk estimator, which forms the basis of the USPSTF recommendation, as well. The evidence is clear that selective use of CAC scoring significantly improves the accuracy of the PCE risk estimator and should be used for additional risk stratification in the appropriate clinical context.
Potential impact of USPSTF interpretation of the evidence
Younger women have typically been characterized as a low-risk patient population; however, they are more likely to have nontraditional risk-enhancing factors, including pregnancy-associated conditions that increase future ASCVD risk, premature menopause and autoimmune diseases that are not captured in the USPSTF recommendations. Over the years, there have been smaller improvements in CV mortality among younger women as compared with other demographic groups, and some studies have even shown an increase in CV death rates in this patient population. Screening for ASCVD risk-enhancing factors that are specific to women can help guide decision-making on statin therapy and improve ASCVD risk reduction in this patient population.
In summary, comprehensive screening of ASCVD risk-enhancing factors and long-term lifestyle modifications for CV health is at the core of contemporary preventive medicine. In the case of statin therapy for primary prevention, reliance on clinical practice recommendations can help clarify the complexities of decision-making while also improving standard of care for ASCVD risk reduction. The 2018 AHA/ACC/Multisociety cholesterol guideline emphasizes that initiation of statin therapy should be patient-specific, and selective CAC scoring can provide personalized more accurate risk assessment, thereby guiding shared-decision making when there is clinical uncertainty about whether to start a long-term medication.
Given the wealth of evidence supporting the benefit of statin therapy for ASCVD risk reduction, it is an overly conservative interpretation of the evidence for the USPSTF to conclude that statin therapy has marked benefit only for patients with a 10-year PCE-estimated risk threshold of 10%. By excluding many patients who would likely otherwise benefit from statin therapy, including those who are younger with multiple risk-enhancing factors, those with borderline ASCVD risk, and those with advanced subclinical atherosclerotic disease, adoption of the USPSTF recommendation will diminish the ability to decrease CV events over the next decade.
References:
- Budoff MJ, et al. Eur Heart J. 2018;doi:10.1093/eurheartj/ehy217.
- Cho L, et al. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.03.060.
- Chou R, et al. JAMA. 2022;doi:10.1001.jama.2022.12138.
- Greenland P, et al. JAMA Cardiol. 2022;doi:10.1001/jamacardio.2022.2638.
- Grundy SM, et al. Circulation. 2018;doi:10.1161/CIR.0000000000000625.
- Gupta K, et al. Prog Cardiovasc Dis. 2022;doi:10.1016/j.pcad.2022.08.007.
- Lloyd-Jones DM, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.07.006.
- Michos ED, et al. N Engl J Med. 2019;doi:10.1056/NEJMra1806939.
- Ni H, et al. Am Heart J. 2009;doi:10.1016/j.ahj.2008.08.016.
- Patel J, et al. JAMA Cardiol. 2021;doi:10.1001/jamacardio.2021.2321.
- Silverman MG, et al. Eur Heart J. 2014;doi:10.1093/eurheartj/eht508.
- Stone NJ, et al. JAMA Cardiol. 2022;doi:10.1001/jamacardio.2022.2851.
- Thanassoulis G, et al. JAMA Cardiol. 2018;doi:10.1001/jamacardio.2018.3476.
- US Preventive Services Task Force. JAMA. 2022;doi:10.1001/jama.2022.13044.
- Virani SS. JAMA Netw Open. 2022;doi:10.1001/jamanetworkopen.2022.28538.
- Zeitouni M, et al. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.06.030.
- Zheng ZJ, et al. Circulation. 2001;doi:10.1161/hc4301.098254.
For more information:
Aardra Rajendran, MD, is a junior assistant resident at Johns Hopkins Medicine. Twitter: @aardrarajendran.
Matthew Belanger, MD, is a cardiovascular disease fellow at Johns Hopkins Medicine.
Neil J. Stone, MD, is the Robert Bonow, MD, professor of medicine (cardiology) and preventive medicine at Northwestern University Feinberg School of Medicine. Twitter: @nstonedoc.
Roger S. Blumenthal, MD, is director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and professor of medicine at Johns Hopkins University School of Medicine. He is also the editor of the Prevention section of the Cardiology Today Editorial Board. Twitter: @rblument1.
The authors can be reached at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Halsted 560, Baltimore, MD 21827.
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