Elsevier

Journal of Clinical Lipidology

Volume 8, Issue 4, July–August 2014, Pages 390-400
Journal of Clinical Lipidology

Original Article
Cascade screening based on genetic testing is cost-effective: Evidence for the implementation of models of care for familial hypercholesterolemia

https://doi.org/10.1016/j.jacl.2014.05.008Get rights and content

Highlights

  • We have examined the cost-effectiveness of cascade screening for FH in Australia.

Background

Familial hypercholesterolemia (FH) imposes significant burden of premature coronary heart disease (CHD).

Objective

This study aimed to determine the cost-effectiveness of FH detection based on genetic testing, supplemented with the measurement of plasma low-density lipoprotein cholesterol concentration, and treatment with statins.

Methods

A Markov model with a 10-year time horizon was constructed to simulate the onset of first-ever CHD and death in close relatives of probands with genetically confirmed FH. The model comprised of 3 health states: “alive without CHD,” “alive with CHD,” and “dead.” Decision-analysis compared the clinical consequences and costs of cascade-screening vs no-screening from an Australian health care perspective. The annual risk of CHD and benefits of treatment was estimated from a cohort study. The underlying prevalence of FH, sensitivity, specificity, cost of screening, treatment, and clinic follow-up visits were derived from a cascade screening service for FH in Western Australia. An annual discount rate of 5% was applied to costs and benefits.

Results

The model estimated that screening for FH would reduce the 10-year incidence of CHD from 50.0% to 25.0% among people with FH. Of every 100 people screened, there was an overall gain of 24.95 life-years and 29.07 quality-adjusted life years (discounted). The incremental cost-effectiveness ratio was in Australian dollars, $4155 per years of life saved and $3565 per quality-adjusted life years gained.

Conclusion

This analysis within an Australian context, demonstrates that cascade screening for FH, using genetic testing supplemented with the measurement of plasma low-density lipoprotein cholesterol concentrations and treatment with statins, is a cost-effective means of preventing CHD in families at risk of FH.

Section snippets

Model structure

Decision analysis12 (Fig. 1) was applied for comparison of screening (screening group) and no screening (no screening group) of the relatives of index cases. Among subjects who had FH (either identified in the screening group or not identified in the no screening group), a Markov model12 with yearly cycles was constructed to simulate the onset of first-ever CHD and death over a 10-year time horizon (Fig. 2). The model comprised 3 health states: (1) “alive without CHD” (in which all subjects

Effectiveness of screening

The results of the base-case analysis showed that cascade screening for FH, assuming an underlying prevalence of FH of 54.3% in the screened population, would prevent 1 CHD event over 10 years for every 7.4 people screened. The number needed to screen (NNS) to prevent one CHD-related death would be 18.3.

Among the 54.3% of people who would have their underlying FH identified, the 10-year incidence of CHD would be reduced from 50.0% to 25.0%, equating to an NNS of 4.0. The predicted 10-year

Discussion

Our analysis suggests that cascade screening for FH using genetic testing supplemented by LDL-C testing, followed by statin treatment, represents a cost-effective means of preventing CHD. Probabilistic sensitivity analysis confirmed that cascade screening strategy followed by treatment was cost-effective in more than 99% of simulations.

A 10-year time horizon is short for patients whose mean age at the time of screening is 42 years. Extending the timeframe of FH model to 20 or 30 years would

Conclusion

Our analysis, based on the modeling of a representative sample of a service program for the detection of FH in an Australian community, clearly demonstrates that cascade screening for FH using a combination of genetic and phenotypic testing represents a cost-effective means of preventing CHD in at-risk families. The data support the recommendations of national and international models of care for FH.6, 13 The results provide a template that could be extended to inform strategies for the

Acknowledgment

The cascade-screening program for FH in Western Australia was funded by the Australia Better Health Initiative and the Department of Health of Western Australia.

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