# Optimization of statin regimens for atherosclerotic cardiovascular disease prevention using polygenic risk scores and real-world evidence

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $595,048

## Abstract

PROJECT SUMMARY/ABSTRACT
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide and statin treatment
remains a cornerstone of cholesterol management guidelines aimed at reducing ASCVD risk. While previous
modifications of these guidelines have increased the number of statin-eligible patients, a lower threshold for
statin eligibility has not been found to improve the number-needed-to-treat (NNT) for ASCVD prevention. A
precision medicine approach that improves both the sensitivity and specificity of statin eligibility criteria in future
guideline revisions (among individuals not currently considered candidates for statins) would be expected to
beneficially reduce NNT. Emerging evidence from genetic substudies of statin randomized controlled trials
(RCTs) demonstrates that coronary heart disease (CHD) polygenic risk scores independently modify statin
relative risk reduction (independent of statin-induced atherogenic cholesterol lowering) in a manner that has the
potential to improve the specificity and sensitivity of statin therapy selection. Furthermore, hypothesis-generating
findings suggest that CHD polygenic risk scores may predict enhanced statin benefit from particular statin types
and doses. However, the generalizability of these results is adversely impacted by lack of heterogeneity in the
RCT study population demographics and statin regimens as well by limited length of patient follow-up and sample
size. Further studies are necessary to better understand how polygenic risk scores modify statin benefit before
this precision medicine tool can be considered for clinical implementation.
Our primary goal in this project is to translate prior proof-of-concept evidence into a clinically-relevant and
actionable tool for use of statins in ASCVD prevention that has the potential to be incorporated into national
guidelines. To accomplish this goal, we will leverage data from the Kaiser Permanente Research Bank (KPRB)
and the Veterans Affairs Million Veteran Program (MVP), which are two of the largest electronic health record-
linked biobanks in the United States. These prospective cohorts are ideal for developing and validating this tool
because they are large (>400,000 participants each), ethnically diverse (~25% historically excluded groups),
have long-term follow-up (>25 years), and contain real-world data (comprehensive electronic health records).
In Aim 1, we will assess the relationship between CHD polygenic risk scores and statin relative risk reduction
for various ASCVD outcomes in diverse populations. In Aim 2, we will determine the extent to which the
association between CHD polygenic risk scores and statin-induced ASCVD risk reduction is related to statin type
and dose. In Aim 3, we will develop a precision medicine tool for statin-induced ASCVD relative risk reduction.
The aims will be carried out by an established multidisciplinary team of experts in clinical pharmacology, clinical
lipidology, cardiova...

## Key facts

- **NIH application ID:** 10683792
- **Project number:** 1R56HL161518-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Akinyemi Oni-Orisan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $595,048
- **Award type:** 1
- **Project period:** 2022-09-12 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683792

## Citation

> US National Institutes of Health, RePORTER application 10683792, Optimization of statin regimens for atherosclerotic cardiovascular disease prevention using polygenic risk scores and real-world evidence (1R56HL161518-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10683792. Licensed CC0.

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