But intensive lifestyle changes are not, according to a modelling study

In young men with LDL-C of ≥130 mg/dL, treatment with statins is highly cost-effective; in young adult women, its cost-efficacy is intermediate, according to a modeling study of elevated LDL-C in young adults. Researchers also found that in young adults, intensive lifestyle interventions to lower LDL-C were not cost-effective.

They published their results in the Journal of the American College of Cardiology.

“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,” wrote Ciaran N. Kohli-Lynch, MD, of Columbia University Irving Medical Center, New York, and fellow researchers.

“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,” they added.

To determine the prevalence of increased LDL-C in young adults in the U.S. with no atherosclerotic cardiovascular disease (ASCVD) and the cost-efficacy of statin treatment and intensive lifestyle modifications, Kohli-Lynch and colleagues conducted this study using data from the U.S. National Health and Nutrition Examination Survey. They created a microsimulation of the CVD Policy model to estimate lifetime health-related quality of life and direct health care costs for LDL-C reduction in this cohort of young adults.

“The CVD Policy Model uses time-varying ASCVD risk factor exposures to simulate an individual’s lifetime risk of ASCVD. As individuals progress through the model, they accumulate health care costs and quality-adjusted life years (QALYs),” researchers explained. “Individuals start the simulation without ASCVD and, each year, are at risk of coronary heart disease (CHD), stroke, combined CHD and stroke, and ASCVD or non-ASCVD death. Incident ASCVD and non-ASCVD mortality risks are estimated using competing risk survival models developed in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study) dataset.”

Young adults were simulated throughout the model from age at enrollment through age 89 or death. Lipid screening was done every five years.

In all, an estimated 26.3 million young adults (27%) in the U.S. without ASCVD had LDL-C of ≥130 mg/dL, and over 8.5 million (95) had levels ≥160 mg/dL. Compared with 86% of adults between the ages of 40-74 years, 51% of young adults have had their cholesterol checked.

Among these young adults, men had a higher mean LDL-C, lower mean HDL-C, higher mean systolic blood pressure, and higher rates of smoking compared with women. Researchers also found the following:

  • Compared with standard care, the addition of treatment with statins in young adults with an LDL-C of ≥130 mg/dL would produce an incremental cost effectiveness ratio (ICER) of $13,200/QUALY, according to modelled projections.
  • Expanding statin eligibility to young men with an LDL-C of ≥130 mg/dL led to an estimated ICER of $31,000/QALY, compared with statins in those with LDL-Cs of ≥160 mg/dL.
  • In young women with LDL-C of ≥160 mg/dL, projections showed that statins—compared with standard care—led to an ICER of $51,500/QALY.
  • Expanding statin eligibility to those with an LDL-C of ≥130 mg/dL made for an ICER of $106,000/QALY.

All lifestyle treatment strategies were predicted to be more costly and less effective compared with statin treatment strategies.

“For men, statin therapy for individuals with an LDL-C of ≥130 mg/dL was projected to be the preferred strategy in 72% of probabilistic simulations at a cost-effectiveness threshold of US$50,000/QALY. At a cost-effectiveness threshold of US$50,000/QALY, standard care had the highest probability (51%) of being the preferred strategy for women. At a higher cost-effectiveness threshold of US$150,000/QALY, however, statin therapy with an LDL-C of ≥130 mg/dL was projected to be the preferred treatment strategy for both men (95%) and women (59%),” wrote researchers.

Upon secondary analysis, Kohli-Lynch and colleagues found that—in both young men and women— statin treatments plus intensive lifestyle intervention with LDL-C ≥160 mg/dL were projected to have higher ICERs and gain less QALYs compared with statin treatment alone. Compared with statin treatment alone, this combination was projected to produce ICERs of $59,300/QALY and $185,000/QALY.

Sensitivity analyses showed that statin strategy cost-efficacy could be improved by using low-price formulations, improving patient adherence, reducing required check-ups, and “averting patient pill-taking disutility.” Intensive lifestyle intervention strategies were affected by discount rate and the number of visits required.

“All treatments were projected to become more effective compared to standard care as the duration of the treatment effect increased. Even when treatment effects were sustained for ≥10 years, statin treatment strategies were more cost-effective than intensive lifestyle interventions,” concluded Kohli-Lynch and fellow researchers.

“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.,” they wrote.

“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),” concluded Kohli-Lynch et al.

In their accompanying editorial, Paul A. Heidenreich, MD, MS, of Stanford University School of Medicine, Palo Alto, Calif., and colleagues ponder the appropriate next steps.

“What might be the impact of preventing the development of elevated LDL-C in the first place? What should be done? First the U.S. Preventive Services Task Force and ACC/AHA should emphasize lifetime risk. In addition to calculating 10-year risk, we should calculate years of life lost (or QALYs lost) from unhealthy LDL-C levels, and both lifestyle and pharmacologic treatment should be considered to treat high LDL-C in adults regardless of age,” they wrote.

“We also need to communicate that the mantra lower is better applies not only to a single measurement but to lifetime exposure to LDL-C. Last, we need to develop methods to study the risks and benefits of early-life interventions, recognizing that traditional randomized controlled trials assessing hard outcomes may not be feasible. Thoughtful cost-effectiveness studies like that of Kohli-Lynch et al help move us toward these goals,” they concluded.

Study limitations include failure to assess alternatives such as population-wide diet and lifestyle programs and statin-related adverse event risks such as statin-induced diabetes, pill-taking disutility, and costs incurred by other statin-related adverse events, and the possibility of lower statin adherence rates in young adults compared with older adults.

  1. Initiating statin treatment in young adults with an LDL-C level of ≥130 mg/dL is highly cost-effective in men and intermediately cost-effective in women, according to a mathematical modeling study.

  2. In young adults, intensive intervention to lower LDL-C through individual lifestyle behavior change is not cost-effective.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

This study was supported by grants from the U.S. National Heart, Lung, and Blood Institute (NHLBI) and the Medical Research Council, Swindon, United Kingdom.

Kohli-Lynch has received a grant from the Medical Research Council.

Heidenreich reported no disclosures.

Cat ID: 102

Topic ID: 74,102,730,102,4,142,192,925