Background: Understanding the real-world impact of clinical trials is important for informing health care policy. This is particularly true when trials are designed to show changes in surrogate endpoints such as changes in risk factors rather than events or mortality. We developed an agent-based microsimulation that estimates the population-level benefits in each US state for cardiometabolic health interventions shown to improve risk factors. Methods: We designed a large-scale, location-specific agent-based simulation model with a population of 51 million in silico individuals and estimated results for the years 2023 to 2040 in 30-day steps for each of the 50 states and District of Columbia. Input data reflected current cardiometabolic health in each state and the effects of interventions and risk factors on outcomes. We constructed three health policy intervention scenarios based on successful randomized controlled trials designed to improve cardiometabolic population health: improved access to fixed-dose combination (FDC) antihypertensive medication, a pharmacist-led intervention to increase adherence to statin and antihypertensives medications at the time they are initiated (Pharmacy), and a community-based lifestyle and behavior intervention designed to prevent diabetes (Community). Outcomes included myocardial infarction, ischemic and non-ischemic heart failure, and ischemic stroke events, deaths, and disability-adjusted life years (DALYs). Results: Our simulation included a representative population of the United States, accurate at the age, sex, and state level, with individual people simulated over 17 years. By the year 2040, the FDC intervention was estimated to have prevented 776,000 (95% UI 578,000?956,000) CVD DALYs and 44,600 (95% UI 32,700?55,600) deaths annually. Reductions in ischemic heart disease deaths accounted for 76.5% of the total reductions in CVD deaths. The Pharmacist intervention prevented 170,000 (95% UI 129,000?208,000) CVD DALYs, and the Community intervention prevented 152,000 (95% UI 128,000?173,000) CVD DALYs. Conclusions: A fixed-dose combination of antihypertensives could prevent 1.2% of total CVD DALYs, with smaller benefits from adherence and lifestyle-focused programs and impact of interventions varying by state. The greatest reduction was in incident myocardial infarctions and ischemic heart disease deaths. Providing accurate population-level estimates at the state level can help local health policy decision-makers implement the most impactful interventions.

The authors have declared no competing interest.

This research was funded by the National Heart, Lung, and Blood Institute. The funders had little input into the design, data, or modeling decisions. They have not read of contributed to this paper.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

N/A This is a simulation study and used only existing data sources.

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