Author + information
- Neil J. Stone, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Neil J. Stone, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair, Suite 600, Chicago, Illinois 60611.
In this issue of the Journal, Navar-Boggan et al. (1) address the strategy for low-risk primary prevention of atherosclerotic cardiovascular disease (ASCVD). This is a thoughtful exploration of the impact of varying the 10-year risk thresholds proposed by the cholesterol guidelines (2) to direct statin assignments in low-risk primary prevention. The authors use data from the Framingham Offspring Study with the acknowledged limitation that it is neither a geographically nor a racially diverse sample. This acknowledgment is important: one of the major advances in risk estimation of the new pooled cohort equations is having a separate risk equation for African-American subjects.
Nonetheless, the authors (1) propose that adjusting a fixed 7.5% threshold for statin assignment in both younger and older eligible subjects could improve the accuracy of such assignments in reducing ASCVD risk. They state “one size doesn’t fit all.” Clinicians should take note: the strategy used by the current prevention guidelines agrees.
What are the characteristics of a good strategy? In a recent book, Rumelt (3) emphasized that a good strategy has a 3-part “kernel.” For those practicing medicine, it begins with a diagnosis that defines or explains the nature of the strategic challenge. There is then a guiding policy and, lastly, a group of coherent actions. As Rumelt noted, “The core of strategy work is always the same: discovering the critical factors in a situation and designing a way of coordinating and focusing actions to deal with those factors.”
The current American College of Cardiology/American Heart Association prevention guidelines addressed a strategic challenge: how to reduce the burden of ASCVD in the United States. The guiding policy for all 4 recent guidelines (lifestyle, obesity, risk assessment, and cholesterol), which were written, presented, and published together, was to create clinical recommendations that flowed directly from detailed evidence reviews based on each panel’s critical questions and to use only quality-rated randomized clinical trials (RCTs) and meta-analyses of RCTs (2,4–6). Each document emphasized counseling on a healthy lifestyle.
One guideline focused on 3 critical questions related to lipid-lowering therapy. Statins emerged as having the strongest evidence for net benefit in high-risk groups. Follow-up lipid testing was recommended, not only to determine the adequacy of the statin effect but also to assess adherence to an optimal lifestyle and the appropriate intensity of statin therapy. A strategic decision was needed, however, for lower risk primary prevention. The threshold for statin treatment of ≥7.5% 10-year ASCVD risk did not indicate automatic statin assignment. The guidelines found evidence to support such a decision, but mindful of the need to individualize therapy, they provide coherent actions to accomplish this.
Although there was evidence for net benefit down to 5% risk based on 3 RCTs with exclusively primary prevention subjects, the guideline panels recommended a 7.5% guidepost, allowing the individual to still derive benefit in case overestimation occurred. Importantly, however, the guidelines recommended a clinician–patient risk discussion preceding the statin assignment in which clinical judgment and informed patient preference could be used to individualize the risk decision. As seen in Figure 1, this discussion should include a review of other risk factors, adherence to optimal lifestyle, the potential for benefit from a statin, the potential for adverse effects/drug–drug interactions, and patient preference.
Furthermore, the risk assessment guideline recommended additional factors that could inform this decision when it was uncertain. These were as follows: family history of premature ASCVD; coronary artery calcium score ≥300 or ≥75th age-, sex-, and race-adjusted percentiles; high sensitivity C-reactive protein levels ≥2.0 mg/l; and an ankle-brachial index <0.9. All these factors increase net reclassification and are especially useful in older subjects. The guidelines panel added low-density lipoprotein cholesterol ≥160 mg/dl and a high lifetime risk of ASCVD to identify younger subjects with genetic dyslipidemia or severe expressions of a single risk factor who could benefit from statin therapy.
Many of the current study’s authors had noted in earlier research that statin prescriptions increase, especially in older adults, if a fixed 7.5% risk threshold is used (7). However, they acknowledged that this was an estimate owing to the recommended risk discussion. The 2013 risk assessment guidelines cautioned that risk assessment is a probabilistic and imperfect exercise (6). However, a study using computed tomography angiography confirmed the benefit of the new guidelines in risk prediction (8). When the computed tomography findings were examined, the current guidelines assigned statins to those with high atherosclerotic burden with greater accuracy than the older guidelines that used low-density lipoprotein cholesterol targets only. Indeed, this study demonstrated that arbitrary targets degrade the ability to assign statins to those who benefit most.
For most of the population, the pooled cohort equations can be used to predict ASCVD risk well, as noted in a representative U.S. community-based sample (9). Although the pooled cohort equations have strong representation from non-Hispanic white and African-American subjects, there were insufficient data for other ethnicities (5). Thus, there are groups in whom over- and underprediction occur. Compared with non-Hispanic white subjects, the estimated 10-year risk of ASCVD may be lower in some Hispanic (e.g., Mexican-American) subjects and some Asian-American (e.g., East Asian ancestry) subjects and higher in American-Indian populations and Asian-American subjects of South Asian ancestry (5,10). In addition, clinicians should consider that low-risk, educated volunteers for clinical trial cohorts, many of whom were health care professionals, also exhibit overestimation by risk assessment (11).
Factors that may result in underprediction include presence of human immunodeficiency virus, solid organ transplantation, and rheumatoid arthritis and other inflammatory disorders. The guidelines specifically target clinician–patient discussions for these groups. Polypharmacy is common in these patients, underscoring the importance of addressing drug–drug interactions.
Thus, after a risk discussion, a 68-year-old subject with optimal or near-optimal risk factors may decide not to receive a statin, even if risk is >7.5%. Conversely, a 45-year-old South-Asian individual with a positive family history may elect statin treatment with a risk score <7.5%.
In conclusion, the clinician–patient discussion offers an opportunity in which these insights, as well as those gleaned from the age- and sex-specific thresholds espoused by Navar-Boggan et al. (1), can be applied. The current guideline’s strategy for reducing ASCVD risk in lower risk primary prevention begins with an estimation of global ASCVD risk. This initiates a risk discussion, leading to a decision that considers RCT evidence, clinician knowledge of the patient’s specific attributes, and informed patient preference. Decision making does not rely exclusively on fixed thresholds but on coherent actions that help achieve the ultimate strategic goal of ASCVD risk reduction.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the, views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Stone has reported that he has no relationships relevant to the contents of this paper to disclose.
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