Integrating Mendelian Randomization With Real-World Evidence: Cost-Effectiveness of Lipoprotein Testing for Primary Prevention of Cardiovascular Disease in High-Income Countries
Author(s)
Jedidiah Morton, PhD1, Florian Kronenberg, MD, PhD2, Magdalena Daccord, MSc3, Nicola Bedlington, MSc4, Albert Wiegman, MD, PhD5, Marius Geanta, MPH, PhD6, Tobias Silberzahn, PhD7, Zhenyue Chen, MPH, PhD8, Bogi Eliasen, MSc9, Mariko Harada-Shiba, MD, PhD10, Marc Rijken, MSc11, George Thanassoulis, MD, MSC, FRCPC12, Zanfina Ademi, MPharm, MPH, PhD13.
1Monash University, Parkville, Australia, 2Medical University of Innsbruck, Innsbruck, Austria, 3FH Europe Foundation, London, United Kingdom, 4European Patients' Forum, Brussels, Belgium, 5FH Europe Foundation, FH Europe Foundation, Netherlands, 6Center for Innovation in Medicine, Bucharest, Romania, 7McKinsey & Company, Frankfurt, Germany, 8Department of Cardiovascular Medicine, Shanghai Ruijin Hospital, Shanhai Jiaotong University School of Medicine,, Shanghai, China, 9Copenhagen Institute for Futures Studies, Copenhagen, Denmark, 10Cardiovascular Center, Osaka Medical and Pharmaceutical University, Osaka, Japan, 11FH Europe Foundation, Netherlands, Netherlands, 12MUHC Preventive and Genomic Cardiology, McGill University, Quebec, QC, Canada, 13Professor, Monash University, Melbourne, Australia.
1Monash University, Parkville, Australia, 2Medical University of Innsbruck, Innsbruck, Austria, 3FH Europe Foundation, London, United Kingdom, 4European Patients' Forum, Brussels, Belgium, 5FH Europe Foundation, FH Europe Foundation, Netherlands, 6Center for Innovation in Medicine, Bucharest, Romania, 7McKinsey & Company, Frankfurt, Germany, 8Department of Cardiovascular Medicine, Shanghai Ruijin Hospital, Shanhai Jiaotong University School of Medicine,, Shanghai, China, 9Copenhagen Institute for Futures Studies, Copenhagen, Denmark, 10Cardiovascular Center, Osaka Medical and Pharmaceutical University, Osaka, Japan, 11FH Europe Foundation, Netherlands, Netherlands, 12MUHC Preventive and Genomic Cardiology, McGill University, Quebec, QC, Canada, 13Professor, Monash University, Melbourne, Australia.
OBJECTIVES: We leverage real-world evidence alongside Mendelian randomisation methods, with lipoprotein(a) screening as a concrete example. Despite that Lp(a) is established causal cardiovascular risk factor, its routine testing has yet to be proven cost-effective. This study therefore assesses for the first time the cost-effectiveness of Lp(a) testing for primary prevention evaluating from both healthcare system and societal perspectives, across multiple countries.
METHODS: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the Systematic Coronary Risk Evaluation 2 (SCORE-2) algorithm. Those with an Lp(a) level ≥105nmol/L (50mg/dL) were treated as high risk (initiation of a statin plus blood pressure lowering). The Lp(a) testing intervention was compared to standard of care. The primary analyses were conducted from the Australian and UK healthcare perspectives in 2023AUD/GBP. A cost adaptation method estimated cost-effectiveness in multiple European countries, Canada, and the USA.
RESULTS: Among 10,000 individuals, 1,807 had their treatment modified from Lp(a) testing. This led to 217 and 255 quality-adjusted life years gained in Australia and the UK, respectively, with corresponding incremental cost-effectiveness ratios of 12,134 (cost-effective) and −3,491 (cost-saving).From a societal perspective, Lp(a) testing saved $85 and 263 per person in Australia and the UK, respectively. Lp(a) testing was cost-saving among all countries tested in the cost adaptation analysis.
CONCLUSIONS: Lp(a) testing in the primary prevention setting is cost-saving and improves CVD risk classification, enabling earlier and more targeted treatment. Routine testing is warranted to prevent avoidable cardiovascular events and reduce healthcare costs.
METHODS: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the Systematic Coronary Risk Evaluation 2 (SCORE-2) algorithm. Those with an Lp(a) level ≥105nmol/L (50mg/dL) were treated as high risk (initiation of a statin plus blood pressure lowering). The Lp(a) testing intervention was compared to standard of care. The primary analyses were conducted from the Australian and UK healthcare perspectives in 2023AUD/GBP. A cost adaptation method estimated cost-effectiveness in multiple European countries, Canada, and the USA.
RESULTS: Among 10,000 individuals, 1,807 had their treatment modified from Lp(a) testing. This led to 217 and 255 quality-adjusted life years gained in Australia and the UK, respectively, with corresponding incremental cost-effectiveness ratios of 12,134 (cost-effective) and −3,491 (cost-saving).From a societal perspective, Lp(a) testing saved $85 and 263 per person in Australia and the UK, respectively. Lp(a) testing was cost-saving among all countries tested in the cost adaptation analysis.
CONCLUSIONS: Lp(a) testing in the primary prevention setting is cost-saving and improves CVD risk classification, enabling earlier and more targeted treatment. Routine testing is warranted to prevent avoidable cardiovascular events and reduce healthcare costs.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD109
Topic
Economic Evaluation, Health Policy & Regulatory, Real World Data & Information Systems
Topic Subcategory
Distributed Data & Research Networks
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), Diabetes/Endocrine/Metabolic Disorders (including obesity)