Lp(a) testing and treatment with Lp(a)-lowering therapies in the primary and secondary prevention of cardiovascular disease in high income countries: A preliminary health technology assessment

Background and Aims: New therapies targeting Lipoprotein (a) (Lp (a) ) are anticipated to enter clinical practice soon. We aimed to estimate the benefits of Lp (a) lowering therapy and threshold price at which treatment with Lp (a) -lowering therapies for people with high Lp (a) in high-risk primary or secondary prevention would be cost-effective from a healthcare and societal perspective using genetic and epidemiological data in the absence of phase III cardiovascular outcome trials. Methods: We constructed and validated a multi-state microsimulation Markov model for primary and secondary prevention populations (n=10, 000 each, selected randomly from the UK Biobank) aged between 40 and 69, followed until age 85 years. Risk of atherosclerotic cardiovascular disease (CVD) was proportional to cumulative Lp (a) and other established cardiovascular (CV) risk factors; risk was adjusted using Mendelian randomisation estimates. We simulated Lp (a) testing of high-risk individuals from the primary and all individuals from the secondary prevention population. Individuals with an Lp (a) level ≥ 192 nmol/L (90 mg/dL) were treated with Lp (a) -lowering therapy that lowered Lp (a) by 97. 5%. The control was standard of care, without Lp (a) -lowering therapy. The primary analyses were conducted from the Australian and UK healthcare and societal perspectives in 2023 AUD and GBP, with annual discounting of 5% (Australia) and 3. 5% (UK). We estimated the effect of varying the threshold for Lp (a) -lowering therapy initiation from 105 nmol/L (50 mg/dL) to 236 nmol/L (110 mg/dL) in scenario analyses. Additional analyses extended to other high-income countries, including Austria, Canada, France, Germany, Italy, The Netherlands, Spain, and the USA. Results: Lp (a) testing and treatment prevented 53 and 306 CV events in the primary and secondary prevention populations (n=10, 000 each), respectively. The maximum annual price at which Lp (a) -lowering therapy would be cost-effective was 250 (Australia) and £150 (UK) in primary and ≥ 6000 (Australia) and £5500 (UK) in secondary prevention populations. Estimated maximum annual prices were similar from the societal perspective and in other high-income countries. In secondary prevention, the number of cardiovascular events prevented increased with a decreasing Lp (a) threshold for initiation of Lp (a) -lowering therapy – 496, 420, 306, and 238 with thresholds of 105 nmol/L (50 mg/dL), 149 nmol/L (70 mg/dL), 192 nmol/L (90 mg/dL; base case) and 236 nmol/L (110 mg/dL), respectively. Conclusion: Novel Lp (a) -lowering therapies are likely to be cost-effective for the secondary prevention of CVD if priced similarly to current siRNA or antibody-based therapies for LDL-C reduction based on the available genetic and epidemiological evidence.