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The American College of Cardiology American Heart Association (ACC/AHA) cholesterol guidelines replaced the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) in 2013,1 a change that was accompanied by significant controversy.2 Notable among the criticisms was that the pooled cohort equations (PCE) overestimates risk and coupled with the relatively lenient risk threshold (10-year PCE ≥7.5%), would unnecessarily increase statin eligibility in the USA. The risk-benefit ratio and cost-effectiveness of this new approach, specifically for primary prevention, was questioned since statins (in addition to preventing cardiovascular disease (CVD) events) have known significant side effects. Pandya and colleagues examine the cost-effectiveness of 10-year risk thresholds for initiation of statins for primary prevention of CVD.
Using a micro simulation model with lifetime horizon, a US societal perspective and a 3% discount rate, a hypothetical cohort of individuals aged 40–75 years from a representative US population received statins, had atherosclerotic (AS) CVD events and died from ASCVD-related or non-ASCVD-related causes, based on natural history and statin treatment parameters. Currently available data, including surveys from NHANES, clinical trials and meta-analyses of treatment, benefits and risks associated with statin therapy were used. The model was calibrated using 16 age-specific and sex-specific coronary heart disease and stroke incidence targets from the Framingham Offspring study. It was validated by comparing model-predicted overall and CVD mortality against observed and predicted mortality data from NHANES III. Sensitivity analyses were performed by varying values for all variables (or group of related variables) through plausible ranges, or using alternative values to assess the robustness of cost-effectiveness analyses to changes in the input parameters.
In the base-case scenario, the current ASCVD threshold of 7.5% or higher—estimated as associated with 48% of adults treated with statins—had an incremental cost-effectiveness ratio (ICER) of US$37 000 per quality-adjusted life-year (QALY) compared with a threshold of 10% or higher. More lenient ASCVD thresholds of 4% or higher (61% of adults treated) and 3% or higher (67% of adults treated) had ICERs of US$81 000/QALY and $140 000/QALY, respectively. Shifting from a 7.5% or higher to a 3% or higher ASCVD risk threshold was associated with an estimated additional 161 560 cardiovascular disease events averted.
This study suggests that the current recommended threshold for statin eligibility (10-year PCE≥7.5%) to prevent primary ASCVD is cost-effective and conservative, contrary to prior criticisms of the ACC/AHA guidelines. Thus, even if PCE overestimates risk, using that metric to determine statin eligibility should avert a large number of ASCVD events, which in monetary terms outweighs the adverse effects. However, is this the same as a favourable risk-benefit ratio for patients eligible for statin therapy for primary prevention? These findings, as important and reassuring as they may be, are only as good as the individual variables included in the cost-effectiveness analysis. The authors clearly state that the cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill a day, statin price and the risk of statin-induced diabetes. The available data on statin compliance and side effects such as diabetes and myopathy are scarce and may be misleading.3 Most clinical trials either exclude participants with statin intolerance or conduct a single-blinded statin run-in phase to exclude participants with statin side effects. Patients enrolled in these trials may also be motivated and hence may minimise reporting of side effects such as myalgia, underestimating the magnitude of the problem. Thus, the true magnitude of statin side effects may be higher, leading to relatively low statin compliance. The odds are in favour of an asymptomatic population-dwelling individual not having an ASCVD event in the next 10 years (relatively low risk) and therefore statin side effects are undesirable. Thus, the goal for primary prevention of ASCVD should not be to cast a wider net so that most of the higher-risk individuals would automatically be included, by lowering the threshold for statin eligibility. Instead, the goal should be to enrich the statin-eligible group with high-risk individuals.
Implications for practice
Despite some limitations, this study was well conducted using the currently available data. These results reassure patients and physicians that at the very least, the approach recommended by the new ACC/AHA cholesterol guidelines for primary prevention may be cost-effective. This study should also curb some criticisms of the new cholesterol guidelines.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.