Cost-Effectiveness of Lipid-Lowering Treatments in Young Adults

Ciaran N. Kohli-Lynch, PHD; Brandon K. Bellows, PHARMD; Yiyi Zhang, PHD; Bonnie Spring, PHD; Dhruv S. Kazi, MD; Mark J. Pletcher, MD; Eric Vittinghoff, PHD; Norrina B. Allen, PHD; Andrew E. Moran, MD

Disclosures

J Am Coll Cardiol. 2021;78(20):1954-1964. 

In This Article

Discussion

In this mathematical modeling study, statin treatment starting in young adulthood at LDL-C thresholds lower than those recommended by current guidelines was projected to prevent or delay ASCVD events and improve population health. Statin therapy was projected to be highly cost-effective for young adult men with an LDL-C of ≥130 mg/dL and intermediately cost-effective for young adult women with an LDL-C of ≥130 mg/dL. The advent of generic pricing has rendered statin treatment highly cost-effective for tens of millions of young adults with raised LDL-C. This result echoes previous findings regarding the increased cost-effectiveness of statin therapy following price reductions.[4,21,28]

To our knowledge, this is the first cost-effectiveness analysis of LDL-C treatment in young adults. Although the efficacy of young adult statin treatment has never been tested in clinical trials, the relationship between cumulative LDL-C exposure earlier in life and later-life ASCVD has been established extensively in observational cohort studies. Cumulative exposure to high LDL-C in young adulthood and middle age have both been shown to significantly increase risk of ASCVD in later life.[3,13,29] When clinical trial evidence is unavailable, simulating decades-long "trials" is a feasible approach to estimating the effectiveness and cost-effectiveness of long-term statin treatment in young adults with raised LDL-C. Our benchmarking exercise found that the dose response we estimated for young adult statin treatment lies between the observed effects of lifelong lower LDL-C (from a mendelian randomization study comparing PCSK9 loss-of-function mutation carriers to noncarriers) and later-life LDL-C lowering (from randomized controlled trials of statin vs placebo).

Our NHANES analysis found that almost one-half of U.S. young adults have never had their cholesterol screened. This aligns with previous estimates of young adult LDL-C screening rates.[30,31] In the United States, many young adults lack health insurance; for those with employer-based or government insurance, lipid screening is not generally reimbursed. Insurance and payment reforms could incentivize young adult lipid screening and treatment. For example, Medicare could reimburse private insurers for treating raised LDL-C in young adults because of anticipated avoided ASCVD events and cost savings when these patients become Medicare eligible. Young adult lipid screening could be expanded efficiently by offering lower-cost screening tests and engaging with community centers or using team-based care to introduce home, worksite, or community-based lipid screening. Additionally, selectively screening young adults with obesity, diabetes, or genetic testing for family history consistent with familial hypercholesterolemia may increase screening and treatment among those at highest risk of ASCVD. However, before investing in expanded statin treatment for young adults, it is important to consider that our previous analysis found treating "borderline" risk adults aged ≥40 years (10-year ASCVD risk: 5.0%-7.4%) is even more cost-effective incremental to standard care than treating young adults with raised LDL-C (Supplemental Table 13).[4]

Greater cost-effectiveness of statin treatment for men has been observed in previous analyses.[4] This differential cost-effectiveness occurred in our analysis because men are at greater lifetime risk of ASCVD than women,[32] and young adult men are more likely to have elevated LDL-C than young adult women. Both LDL-C levels and cholesterol screening rates vary across racial subgroups of U.S. young adults (Supplemental Table 14). Further research should establish the impact of young adult lipid-lowering screening and treatment strategies on racial disparities in health.

Study Limitations

Our results suggest that intensive intervention to lower LDL-C through individual lifestyle behavior change is not cost-effective. However, we did not evaluate the alternative of population-wide diet and lifestyle programs, which have been highly effective in lowering LDL-C and improving population health.[33] Alternative approaches that systematically optimize behavioral "treatment packages" may help establish more cost-effective and sustainable behavioral treatments for lowering LDL-C.[34,35]

Although young adult lipid lowering could lead to lifetime health gains for eligible patients, there may be long-term statin-related adverse event risks that we have not accounted for. In middle-aged adults, long-term statins present a favorable profile when risks are weighed against benefits.[36–38] Our analysis accounted for the risk of statin-induced diabetes, pill-taking disutility, and costs related to other major and minor statin-related adverse events. In sensitivity analyses, our results were robust to assumptions regarding the incidence and impact of statin-related adverse events. Nonetheless, we may have underestimated how intolerable daily pill-taking is for young adults. Although there is limited evidence on statin adherence in ASCVD-free young adults, our estimate aligns with reported adherence rates in young adults with high LDL-C and individuals who experienced "extremely premature" ASCVD.[39,40] Statin adherence rates may be lower in young adults compared with older adults, and we explored alternative adherence rates in sensitivity analyses. A practical and more patient-centered approach to young adult lipid lowering may require the development of once- or twice-yearly treatments (as seen with newer, experimental PCSK9 inhibitor agents) and making them low cost.

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