Department of Medicine, University of Toronto, Toronto (M.K.).
Population Health Research Institute (M.K., A.L., S.M., R.L., S.N., G.P.), McMaster University, Hamilton, Ontario, Canada.
Circ Genom Precis Med. 2022 Oct;15(5):e003423. doi: 10.1161/CIRCGEN.121.003423. Epub 2022 Jul 29.
Atherosclerotic cardiovascular diseases (CVDs) are leading causes of death despite effective therapies and result in unnecessary morbidity and mortality throughout the world. We aimed to investigate the cost-effectiveness of polygenic risk scores (PRS) to guide statin therapy for Canadians with intermediate CVD risk and model its economic outlook.
This cost-utility analysis was conducted using UK Biobank prospective cohort study participants, with recruitment from 2006 to 2010, and at least 10 years of follow-up. We included nonrelated white British-descent participants (n=96 116) at intermediate CVD risk with no prior lipid lowering medication or statin-indicated conditions. A coronary artery disease PRS was used to inform decision to use statins. The effects of statin therapy with and without PRS, as well as CVD events were modelled to determine the incremental cost-effectiveness ratio from a Canadian public health care perspective. We discounted future costs and quality-adjusted life-years by 1.5% annually.
The optimal economic strategy was when intermediate risk individuals with a PRS in the top 70% are eligible for statins while the lowest 1% are excluded. Base-case analysis at a genotyping cost of $70 produced an incremental cost-effectiveness ratio of $172 906 (143 685 USD) per quality-adjusted life-year. In the probabilistic sensitivity analysis, the intervention has approximately a 50% probability of being cost-effective at $179 100 (148 749 USD) per quality-adjusted life-year. At a $0 genotyping cost, representing individuals with existing genotyping information, PRS-guided strategies dominated standard care when 12% of the lowest PRS individuals were withheld from statins. With improved PRS predictive performance and lower genotyping costs, the incremental cost-effectiveness ratio demonstrates possible cost-effectiveness under thresholds of $150 000 and possibly $50 000 per quality-adjusted life-year.
This study suggests that using PRS alongside existing guidelines might be cost-effective for CVD. Stronger predictiveness combined with decreased cost of PRS could further improve cost-effectiveness, providing an economic basis for its inclusion into clinical care.
尽管有有效的治疗方法，但动脉粥样硬化性心血管疾病（CVD）仍是主要的死亡原因，导致全世界出现不必要的发病率和死亡率。我们旨在研究多基因风险评分（PRS）指导他汀类药物治疗加拿大中等 CVD 风险患者的成本效益，并对其经济前景进行建模。
本成本效用分析使用英国生物库前瞻性队列研究参与者，招募时间为 2006 年至 2010 年，随访时间至少 10 年。我们纳入了无降脂药物治疗或他汀类药物适应证的无既往血脂异常的中等 CVD 风险的非相关白种英国血统参与者（n=96116）。使用冠心病 PRS 来决定是否使用他汀类药物。他汀类药物治疗的效果以及有无 PRS 和 CVD 事件都进行了建模，以确定从加拿大公共卫生保健角度的增量成本效益比。我们按 1.5%的年贴现率贴现未来成本和质量调整生命年。
最优的经济策略是将 PRS 在前 70%的中等风险个体纳入他汀类药物治疗，而将最低的 1%排除在外。在基因分型成本为 70 美元的基础案例分析中，每质量调整生命年的增量成本效益比为 172906 美元（143685 美元）。在概率敏感性分析中，在每质量调整生命年 179100 美元（148749 美元）的成本效益阈值下，该干预措施具有约 50%的成本效益概率。在基因分型成本为 0 美元的情况下，PRS 指导的策略在将最低 PRS 个体中的 12%排除在他汀类药物治疗之外时，代表了具有现有基因分型信息的个体，这一策略占据主导地位。随着 PRS 预测性能的提高和基因分型成本的降低，增量成本效益比在每质量调整生命年 150000 美元和可能 50000 美元的阈值下显示出可能的成本效益。
本研究表明，在现有指南的基础上使用 PRS 可能对 CVD 具有成本效益。更强的预测能力结合 PRS 成本的降低可以进一步提高成本效益，为其纳入临床护理提供经济依据。
