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Reducing Sex Disparities in Statin Therapy Among Female Veterans With Type 2 Diabetes and/or Cardiovascular Disease
Cardiovascular disease (CVD) is the leading cause of death among women in the United States.1 Most CVD is due to the buildup of plaque (ie, cholesterol, proteins, calcium, and inflammatory cells) in artery walls.2 The plaque may lead to atherosclerotic cardiovascular disease (ASCVD), which includes coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerotic disease.2,3 Control and reduction of ASCVD risk factors, including high cholesterol levels, elevated blood pressure, insulin resistance, smoking, and a sedentary lifestyle, can contribute to a reduction in ASCVD morbidity and mortality.2 People with type 2 diabetes mellitus (T2DM) have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD.4,5
The prescribing of statins (3-hydroxy-3-methyl-glutaryl-coenzmye A reductase inhibitors) is the cornerstone of lipid-lowering therapy and cardiovascular risk reduction for primary and secondary prevention of ASCVD.6 The American Diabetes Association (ADA) and American College of Cardiology/American Heart Association (ACC/AHA) recommend moderate- to high-intensity statins for primary prevention in patients with T2DM and high-intensity statins for secondary prevention in those with or without diabetes when not contraindicated.4,5,7 Despite eligibility according to guideline recommendations, research predominantly shows that women are less likely to receive statin therapy; however, this trend is improving. [6,8-11] To explain the sex differences in statin use, Nanna et al found that there is a combination of women being offered statin therapy less frequently, declining therapy more frequently, and discontinuing treatment more frequently.11 One possibility for discontinuing treatment could be statin-associated muscle symptoms (SAMS), which occur in about 10% of patients.12 The incidence of adverse effects (AEs) may be related to the way statins are metabolized.
Pharmacogenomic testing is free for veterans through the US Department of Veterans Affairs (VA) PHASER program, which offers information and recommendations for a panel of 11 gene variants. The panel includes genes related to common medication classes such as anticoagulants, antiplatelets, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, opioids, antidepressants, and statins. The VA PHASER panel includes the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, which is predominantly expressed in the liver and facilitates the hepatic uptake of most statins.13,14 A reduced function of SLCO1B1 can lead to higher statin levels, resulting in increased concentrations that may potentially cause SAMS.13,14 Some alleles associated with reduced function include SLCO1B1*5, *15, *23, *31, and *46 to *49, whereas others are associated with increased function, such as SLCO1B1 *14 and *20 (Appendix).15 Supporting evidence shows the SLCO1B1*5 nucleotide polymorphism increases plasma levels of simvastatin and atorvastatin, affecting effectiveness or toxicity. 13 Females tend to have a lower body weight and higher percentage of body fat compared with males, which might lead to higher concentrations of lipophilic drugs, including atorvastatin and simvastatin, which may be exacerbated by decreased function of SLCO1B1*5.15 With pharmacogenomic testing, therapeutic recommendations can be made to improve the overall safety and efficacy of statins, thus improving adherence using a patient-specific approach.14,15
Methods
Carl Vinson VA Medical Center (CVVAMC) serves about 42,000 veterans in Central and South Georgia, of which about 15% are female. Of the female veterans enrolled in care, 63% identify as Black, 27% White, and 1.5% as Asian, American Indian/Alaska Native, or Native Hawaiian/Other Pacific Islander. The 2020 Veterans Chartbook report showed that female veterans and minority racial and ethnic groups had worse access to health care and higher mortality rates than their male and non-Hispanic White counterparts.16
The Primary Care Equity Dashboard (PCED) was developed to engage the VA health care workforce in the process of identifying and addressing inequities in local patient populations.17 Using electronic quality measure data, the PCED provides Veterans Integrated Service Network-level and facility-level performance on several metrics.18 The PCED had not been previously used at the CVVAMC, and few publications or quality improvement projects regarding its use have been reported by the VA Office of Health Equity. PCED helped identify disparities when comparing female to male patients in the prescribing of statin therapy for patients with CVD and statin therapy for patients with T2DM.
VA PHASER pharmacogenomic analyses provided an opportunity to expand this quality improvement project. Sanford Health and the VA collaborated on the PHASER program to offer free genetic testing for veterans. The program launched in 2019 and expanded to various VA sites, including CVVAMC in March 2023. This program has been extended to December 31, 2025.
The primary objective of this quality improvement project was to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk. Secondary outcomes included increased pharmacogenomic testing and the assessment of pharmacogenomic results related to statin therapy. This project was approved by the CVVAMC Pharmacy and Therapeutics Committee. The PCED was used to identify female veterans with T2DM and/or CVD without an active prescription for a statin between July and October 2023. A review of Computerized Patient Record System patient charts was completed to screen for prespecified inclusion and exclusion criteria. Veterans were included if they were assigned female at birth, were enrolled in care at CVVAMC, and had a diagnosis of T2DM or CVD (history of myocardial infarction, coronary bypass graft, percutaneous coronary intervention, or other revascularization in any setting).
Veterans were excluded if they were currently pregnant, trying to conceive, breastfeeding, had a T1DM diagnosis, had previously documented hypersensitivity to a statin, active liver failure or decompensated cirrhosis, previously documented statin-associated rhabdomyolysis or autoimmune myopathy, an active prescription for a proprotein convertase subtilisin/kexin type 9 inhibitor, or previously documented statin intolerance (defined as the inability to tolerate ≥ 3 statins, with ≥ 1 prescribed at low intensity or alternate-day dosing). The female veterans were compared to 2 comparators: the facility's male veterans and the VA national average, identified via the PCED.
Once a veteran was screened, they were telephoned between October 2023 and February 2024 and provided education on statin use and pharmacogenomic testing using a standardized note template. An order was placed for participants who provided verbal consent for pharmacogenomic testing. Those who agreed to statin initiation were referred to a clinical pharmacist practitioner (CPP) who contacted them at a later date to prescribe a statin following the recommendations of the 2019 ACC/AHA and 2023 ADA guidelines and pharmacogenomic testing, if applicable.4,5,7 Appropriate monitoring and follow-up occurred at the discretion of each CPP. Data collection included: age, race, diagnoses (T2DM, CVD, or both), baseline lipid panel (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), hepatic function, name and dose of statin, reasons for declining statin therapy, and pharmacogenomic testing results related to SLCO1B1.
Results
At baseline in July 2023, 77.8% of female veterans with T2DM were prescribed a statin, which exceeded the national VA average (77.0%), but was below the rate for male veterans (78.7%) in the facility comparator group.17 Additionally, 82.2% of females with CVD were prescribed a statin, which was below the national VA average of 86.0% and the 84.9% of male veterans in the facility comparator group.17 The PCED identified 189 female veterans from July 2023 to October 2023 who may benefit from statin therapy. Thirty-three females met the exclusion criteria. Of the 156 included veterans, 129 (82.7%) were successfully contacted and 27 (17.3%) could not be reached by telephone after 3 attempts (Figure 1). The 129 female veterans contacted had a mean age of 59 years and the majority were Black (82.9%) (Table 1).
Abbreviations: CVD, cardiovascular disease; PCSK9, proprotein convertase subtilisin/
kexin type 9; T2DM, type 2 diabetes mellitus; VAMC, Veterans Affairs medical center.
Primary Outcomes
Of the 129 contacted veterans, 31 (24.0%) had a non-VA statin prescription, 13 (10.1%) had an active VA statin prescription, and 85 (65.9%) did not have a statin prescription, despite being eligible. Statin adherence was confirmed with participants, and the medication list was updated accordingly.
Of the 85 veterans with no active statin therapy, 37 (43.5%) accepted a new statin prescription and 48 (56.5%) declined. There were various reasons provided for declining statin therapy: 17 participants (35.4%) declined due to concern for AEs (Table 2).
From July 2023 to March 2024, the percentage of female veterans with active statin therapy with T2DM increased from 77.8% to 79.0%. For those with active statin therapy with CVD, usage increased from 82.2% to 90.2%, which exceeded the national VA average and facility male comparator group (Figures 2 and 3).17
Secondary Outcomes
Seventy-one of 129 veterans (55.0%) gave verbal consent, and 47 (66.2%) completed the pharmacogenomic testing; 58 (45.0%) declined. Five veterans (10.6%) had a known SLCO1B1 allele variant present. One veteran required a change in statin therapy based on the results (eAppendix).
Discussion
This project aimed to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk and increase pharmacogenomic testing using the PCED and care managed by CPPs. The results of this quality improvement project illustrated that both metrics have improved at CVVAMC as a result of the intervention. The results in both metrics now exceed the PCED national VA average, and the CVD metric also exceeds that of the facility male comparator group. While there was only a 1.2% increase from July 2023 to March 2024 for patients with T2DM, there was an 8.0% increase for patients with CVD. Despite standardized education on statin use, more veterans declined therapy than accepted it, mostly due to concern for AEs. Recording the reasons for declining statin therapy offered valuable insight that can be used in additional discussions with veterans and clinicians.
Pharmacogenomics gives clinicians the unique opportunity to take a proactive approach to better predict drug responses, potentially allowing for less trial and error with medications, fewer AEs, greater trust in the clinician, and improved medication adherence. The CPPs incorporated pharmacogenomic testing into their practice, which led to identifying 5 SLCO1B1 gene abnormalities. The PCED served as a powerful tool for advancing equity-focused quality improvement initiatives on a local level and was crucial in prioritizing the detection of veterans potentially receiving suboptimal care.
Limitations
The nature of “cold calls” made it challenging to establish contact for inclusion in this study. An alternative to increase engagement could have been scheduled phone or face-to-face visits. While the use of the PCED was crucial, data did not account for statins listed in the non-VA medication list. All 31 patients with statins prescribed outside the VA had a start date added to provide the most accurate representation of the data moving forward.
Another limitation in this project was its small sample size and population. CVVAMC serves about 6200 female veterans, with roughly 63% identifying as Black. The preponderance of Black individuals (83%) in this project is typical for the female patient population at CVVAMC but may not reflect the demographics of other populations. Other limitations to this project consisted of scheduling conflicts. Appointments for laboratory draws at community-based outpatient clinics were subject to availability, which resulted in some delay in completion of pharmacogenomic testing.
Conclusions
CPPs can help reduce inequity in health care delivery. Increased incorporation of the PCED into regular practice within the VA is recommended to continue addressing sex disparities in statin use, diabetes control, blood pressure management, cancer screenings, and vaccination needs. CVVAMC plans to expand its use through another quality improvement project focused on reducing sex disparities in blood pressure management. Improving educational resources made available to veterans on the importance of statin therapy and potential to mitigate AEs through use of the VA PHASER program also would be helpful. This project successfully improved CVVAMC metrics for female veterans appropriately prescribed statin therapy and increased access to pharmacogenomic testing. Most importantly, it helped close the sex-based gap in CVD risk reduction care.
- Heron M. Deaths: leading causes for 2018. Nat Vital Stat Rep. 2021;70:1-114.
- US Department of Veterans Affairs, US Department of Defense. VA/DoD Clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction. Published June 2020. Accessed August 25, 2025. https://www.healthquality.va.gov/guidelines/CD/lipids/VADODDyslipidemiaCPG5087212020.pdf
- Atherosclerotic Cardiovascular Disease (ASCVD). American Heart Association. Accessed August 26, 2025. https:// www.heart.org/en/professional/quality-improvement/ascvd
- American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S144-S174. doi:10.2337/dc22-S010
- American Diabetes Association. Standards of Care in Diabetes— 2023 abridged for primary care providers. Clinical Diabetes. 2022;41(1):4-31. doi:10.2337/cd23-as01
- Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115:21-26. doi:10.1016/j.amjcard.2014.09.041
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/ AHA Guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
- Buchanan CH, Brown EA, Bishu KG, et al. The magnitude and potential causes of gender disparities in statin therapy in veterans with type 2 diabetes: a 10-year nationwide longitudinal cohort study. Womens Health Issues. 2022;32:274-283. doi:10.1016/j.whi.2021.10.003
- Ahmed F, Lin J, Ahmed T, et al. Health disparities: statin prescribing patterns among patients with diabetes in a family medicine clinic. Health Equity. 2022;6:291-297. doi:10.1089/heq.2021.0144
- Metser G, Bradley C, Moise N, Liyanage-Don N, Kronish I, Ye S. Gaps and disparities in primary prevention statin prescription during outpatient care. Am J Cardiol. 2021;161:36-41. doi:10.1016/j.amjcard.2021.08.070
- Nanna MG, Wang TY, Xiang Q, et al. Sex differences in the use of statins in community practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562. doi:10.1161/CIRCOUTCOMES.118.005562
- Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016;9:97-106. doi:10.2147/PGPM.S86013
- Türkmen D, Masoli JAH, Kuo CL, Bowden J, Melzer D, Pilling LC. Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men. Br J Clin Pharmacol. 2022;88:3230-3240. doi:10.1111/bcp.15245
- Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111:1007-1021. doi:10.1002/cpt.2557
- Ramsey LB, Gong L, Lee SB, et al. PharmVar GeneFocus: SLCO1B1. Clin Pharmacol Ther. 2023;113:782-793. doi:10.1002/cpt.2705
- National Healthcare Quality and Disparities Report: Chartbook on Healthcare for Veterans. Rockville (MD): Agency for Healthcare Research and Quality (US); November 2020.
- Procario G. Primary Care Equity Dashboard [database online]. Power Bi. 2023. Accessed August 26, 2025. https://app.powerbigov.us
- Hausmann LRM, Lamorte C, Estock JL. Understanding the context for incorporating equity into quality improvement throughout a national health care system. Health Equity. 2023;7(1):312-320. doi:10.1089/heq.2023.0009
Cardiovascular disease (CVD) is the leading cause of death among women in the United States.1 Most CVD is due to the buildup of plaque (ie, cholesterol, proteins, calcium, and inflammatory cells) in artery walls.2 The plaque may lead to atherosclerotic cardiovascular disease (ASCVD), which includes coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerotic disease.2,3 Control and reduction of ASCVD risk factors, including high cholesterol levels, elevated blood pressure, insulin resistance, smoking, and a sedentary lifestyle, can contribute to a reduction in ASCVD morbidity and mortality.2 People with type 2 diabetes mellitus (T2DM) have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD.4,5
The prescribing of statins (3-hydroxy-3-methyl-glutaryl-coenzmye A reductase inhibitors) is the cornerstone of lipid-lowering therapy and cardiovascular risk reduction for primary and secondary prevention of ASCVD.6 The American Diabetes Association (ADA) and American College of Cardiology/American Heart Association (ACC/AHA) recommend moderate- to high-intensity statins for primary prevention in patients with T2DM and high-intensity statins for secondary prevention in those with or without diabetes when not contraindicated.4,5,7 Despite eligibility according to guideline recommendations, research predominantly shows that women are less likely to receive statin therapy; however, this trend is improving. [6,8-11] To explain the sex differences in statin use, Nanna et al found that there is a combination of women being offered statin therapy less frequently, declining therapy more frequently, and discontinuing treatment more frequently.11 One possibility for discontinuing treatment could be statin-associated muscle symptoms (SAMS), which occur in about 10% of patients.12 The incidence of adverse effects (AEs) may be related to the way statins are metabolized.
Pharmacogenomic testing is free for veterans through the US Department of Veterans Affairs (VA) PHASER program, which offers information and recommendations for a panel of 11 gene variants. The panel includes genes related to common medication classes such as anticoagulants, antiplatelets, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, opioids, antidepressants, and statins. The VA PHASER panel includes the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, which is predominantly expressed in the liver and facilitates the hepatic uptake of most statins.13,14 A reduced function of SLCO1B1 can lead to higher statin levels, resulting in increased concentrations that may potentially cause SAMS.13,14 Some alleles associated with reduced function include SLCO1B1*5, *15, *23, *31, and *46 to *49, whereas others are associated with increased function, such as SLCO1B1 *14 and *20 (Appendix).15 Supporting evidence shows the SLCO1B1*5 nucleotide polymorphism increases plasma levels of simvastatin and atorvastatin, affecting effectiveness or toxicity. 13 Females tend to have a lower body weight and higher percentage of body fat compared with males, which might lead to higher concentrations of lipophilic drugs, including atorvastatin and simvastatin, which may be exacerbated by decreased function of SLCO1B1*5.15 With pharmacogenomic testing, therapeutic recommendations can be made to improve the overall safety and efficacy of statins, thus improving adherence using a patient-specific approach.14,15
Methods
Carl Vinson VA Medical Center (CVVAMC) serves about 42,000 veterans in Central and South Georgia, of which about 15% are female. Of the female veterans enrolled in care, 63% identify as Black, 27% White, and 1.5% as Asian, American Indian/Alaska Native, or Native Hawaiian/Other Pacific Islander. The 2020 Veterans Chartbook report showed that female veterans and minority racial and ethnic groups had worse access to health care and higher mortality rates than their male and non-Hispanic White counterparts.16
The Primary Care Equity Dashboard (PCED) was developed to engage the VA health care workforce in the process of identifying and addressing inequities in local patient populations.17 Using electronic quality measure data, the PCED provides Veterans Integrated Service Network-level and facility-level performance on several metrics.18 The PCED had not been previously used at the CVVAMC, and few publications or quality improvement projects regarding its use have been reported by the VA Office of Health Equity. PCED helped identify disparities when comparing female to male patients in the prescribing of statin therapy for patients with CVD and statin therapy for patients with T2DM.
VA PHASER pharmacogenomic analyses provided an opportunity to expand this quality improvement project. Sanford Health and the VA collaborated on the PHASER program to offer free genetic testing for veterans. The program launched in 2019 and expanded to various VA sites, including CVVAMC in March 2023. This program has been extended to December 31, 2025.
The primary objective of this quality improvement project was to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk. Secondary outcomes included increased pharmacogenomic testing and the assessment of pharmacogenomic results related to statin therapy. This project was approved by the CVVAMC Pharmacy and Therapeutics Committee. The PCED was used to identify female veterans with T2DM and/or CVD without an active prescription for a statin between July and October 2023. A review of Computerized Patient Record System patient charts was completed to screen for prespecified inclusion and exclusion criteria. Veterans were included if they were assigned female at birth, were enrolled in care at CVVAMC, and had a diagnosis of T2DM or CVD (history of myocardial infarction, coronary bypass graft, percutaneous coronary intervention, or other revascularization in any setting).
Veterans were excluded if they were currently pregnant, trying to conceive, breastfeeding, had a T1DM diagnosis, had previously documented hypersensitivity to a statin, active liver failure or decompensated cirrhosis, previously documented statin-associated rhabdomyolysis or autoimmune myopathy, an active prescription for a proprotein convertase subtilisin/kexin type 9 inhibitor, or previously documented statin intolerance (defined as the inability to tolerate ≥ 3 statins, with ≥ 1 prescribed at low intensity or alternate-day dosing). The female veterans were compared to 2 comparators: the facility's male veterans and the VA national average, identified via the PCED.
Once a veteran was screened, they were telephoned between October 2023 and February 2024 and provided education on statin use and pharmacogenomic testing using a standardized note template. An order was placed for participants who provided verbal consent for pharmacogenomic testing. Those who agreed to statin initiation were referred to a clinical pharmacist practitioner (CPP) who contacted them at a later date to prescribe a statin following the recommendations of the 2019 ACC/AHA and 2023 ADA guidelines and pharmacogenomic testing, if applicable.4,5,7 Appropriate monitoring and follow-up occurred at the discretion of each CPP. Data collection included: age, race, diagnoses (T2DM, CVD, or both), baseline lipid panel (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), hepatic function, name and dose of statin, reasons for declining statin therapy, and pharmacogenomic testing results related to SLCO1B1.
Results
At baseline in July 2023, 77.8% of female veterans with T2DM were prescribed a statin, which exceeded the national VA average (77.0%), but was below the rate for male veterans (78.7%) in the facility comparator group.17 Additionally, 82.2% of females with CVD were prescribed a statin, which was below the national VA average of 86.0% and the 84.9% of male veterans in the facility comparator group.17 The PCED identified 189 female veterans from July 2023 to October 2023 who may benefit from statin therapy. Thirty-three females met the exclusion criteria. Of the 156 included veterans, 129 (82.7%) were successfully contacted and 27 (17.3%) could not be reached by telephone after 3 attempts (Figure 1). The 129 female veterans contacted had a mean age of 59 years and the majority were Black (82.9%) (Table 1).
Abbreviations: CVD, cardiovascular disease; PCSK9, proprotein convertase subtilisin/
kexin type 9; T2DM, type 2 diabetes mellitus; VAMC, Veterans Affairs medical center.
Primary Outcomes
Of the 129 contacted veterans, 31 (24.0%) had a non-VA statin prescription, 13 (10.1%) had an active VA statin prescription, and 85 (65.9%) did not have a statin prescription, despite being eligible. Statin adherence was confirmed with participants, and the medication list was updated accordingly.
Of the 85 veterans with no active statin therapy, 37 (43.5%) accepted a new statin prescription and 48 (56.5%) declined. There were various reasons provided for declining statin therapy: 17 participants (35.4%) declined due to concern for AEs (Table 2).
From July 2023 to March 2024, the percentage of female veterans with active statin therapy with T2DM increased from 77.8% to 79.0%. For those with active statin therapy with CVD, usage increased from 82.2% to 90.2%, which exceeded the national VA average and facility male comparator group (Figures 2 and 3).17
Secondary Outcomes
Seventy-one of 129 veterans (55.0%) gave verbal consent, and 47 (66.2%) completed the pharmacogenomic testing; 58 (45.0%) declined. Five veterans (10.6%) had a known SLCO1B1 allele variant present. One veteran required a change in statin therapy based on the results (eAppendix).
Discussion
This project aimed to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk and increase pharmacogenomic testing using the PCED and care managed by CPPs. The results of this quality improvement project illustrated that both metrics have improved at CVVAMC as a result of the intervention. The results in both metrics now exceed the PCED national VA average, and the CVD metric also exceeds that of the facility male comparator group. While there was only a 1.2% increase from July 2023 to March 2024 for patients with T2DM, there was an 8.0% increase for patients with CVD. Despite standardized education on statin use, more veterans declined therapy than accepted it, mostly due to concern for AEs. Recording the reasons for declining statin therapy offered valuable insight that can be used in additional discussions with veterans and clinicians.
Pharmacogenomics gives clinicians the unique opportunity to take a proactive approach to better predict drug responses, potentially allowing for less trial and error with medications, fewer AEs, greater trust in the clinician, and improved medication adherence. The CPPs incorporated pharmacogenomic testing into their practice, which led to identifying 5 SLCO1B1 gene abnormalities. The PCED served as a powerful tool for advancing equity-focused quality improvement initiatives on a local level and was crucial in prioritizing the detection of veterans potentially receiving suboptimal care.
Limitations
The nature of “cold calls” made it challenging to establish contact for inclusion in this study. An alternative to increase engagement could have been scheduled phone or face-to-face visits. While the use of the PCED was crucial, data did not account for statins listed in the non-VA medication list. All 31 patients with statins prescribed outside the VA had a start date added to provide the most accurate representation of the data moving forward.
Another limitation in this project was its small sample size and population. CVVAMC serves about 6200 female veterans, with roughly 63% identifying as Black. The preponderance of Black individuals (83%) in this project is typical for the female patient population at CVVAMC but may not reflect the demographics of other populations. Other limitations to this project consisted of scheduling conflicts. Appointments for laboratory draws at community-based outpatient clinics were subject to availability, which resulted in some delay in completion of pharmacogenomic testing.
Conclusions
CPPs can help reduce inequity in health care delivery. Increased incorporation of the PCED into regular practice within the VA is recommended to continue addressing sex disparities in statin use, diabetes control, blood pressure management, cancer screenings, and vaccination needs. CVVAMC plans to expand its use through another quality improvement project focused on reducing sex disparities in blood pressure management. Improving educational resources made available to veterans on the importance of statin therapy and potential to mitigate AEs through use of the VA PHASER program also would be helpful. This project successfully improved CVVAMC metrics for female veterans appropriately prescribed statin therapy and increased access to pharmacogenomic testing. Most importantly, it helped close the sex-based gap in CVD risk reduction care.
Cardiovascular disease (CVD) is the leading cause of death among women in the United States.1 Most CVD is due to the buildup of plaque (ie, cholesterol, proteins, calcium, and inflammatory cells) in artery walls.2 The plaque may lead to atherosclerotic cardiovascular disease (ASCVD), which includes coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerotic disease.2,3 Control and reduction of ASCVD risk factors, including high cholesterol levels, elevated blood pressure, insulin resistance, smoking, and a sedentary lifestyle, can contribute to a reduction in ASCVD morbidity and mortality.2 People with type 2 diabetes mellitus (T2DM) have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD.4,5
The prescribing of statins (3-hydroxy-3-methyl-glutaryl-coenzmye A reductase inhibitors) is the cornerstone of lipid-lowering therapy and cardiovascular risk reduction for primary and secondary prevention of ASCVD.6 The American Diabetes Association (ADA) and American College of Cardiology/American Heart Association (ACC/AHA) recommend moderate- to high-intensity statins for primary prevention in patients with T2DM and high-intensity statins for secondary prevention in those with or without diabetes when not contraindicated.4,5,7 Despite eligibility according to guideline recommendations, research predominantly shows that women are less likely to receive statin therapy; however, this trend is improving. [6,8-11] To explain the sex differences in statin use, Nanna et al found that there is a combination of women being offered statin therapy less frequently, declining therapy more frequently, and discontinuing treatment more frequently.11 One possibility for discontinuing treatment could be statin-associated muscle symptoms (SAMS), which occur in about 10% of patients.12 The incidence of adverse effects (AEs) may be related to the way statins are metabolized.
Pharmacogenomic testing is free for veterans through the US Department of Veterans Affairs (VA) PHASER program, which offers information and recommendations for a panel of 11 gene variants. The panel includes genes related to common medication classes such as anticoagulants, antiplatelets, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, opioids, antidepressants, and statins. The VA PHASER panel includes the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, which is predominantly expressed in the liver and facilitates the hepatic uptake of most statins.13,14 A reduced function of SLCO1B1 can lead to higher statin levels, resulting in increased concentrations that may potentially cause SAMS.13,14 Some alleles associated with reduced function include SLCO1B1*5, *15, *23, *31, and *46 to *49, whereas others are associated with increased function, such as SLCO1B1 *14 and *20 (Appendix).15 Supporting evidence shows the SLCO1B1*5 nucleotide polymorphism increases plasma levels of simvastatin and atorvastatin, affecting effectiveness or toxicity. 13 Females tend to have a lower body weight and higher percentage of body fat compared with males, which might lead to higher concentrations of lipophilic drugs, including atorvastatin and simvastatin, which may be exacerbated by decreased function of SLCO1B1*5.15 With pharmacogenomic testing, therapeutic recommendations can be made to improve the overall safety and efficacy of statins, thus improving adherence using a patient-specific approach.14,15
Methods
Carl Vinson VA Medical Center (CVVAMC) serves about 42,000 veterans in Central and South Georgia, of which about 15% are female. Of the female veterans enrolled in care, 63% identify as Black, 27% White, and 1.5% as Asian, American Indian/Alaska Native, or Native Hawaiian/Other Pacific Islander. The 2020 Veterans Chartbook report showed that female veterans and minority racial and ethnic groups had worse access to health care and higher mortality rates than their male and non-Hispanic White counterparts.16
The Primary Care Equity Dashboard (PCED) was developed to engage the VA health care workforce in the process of identifying and addressing inequities in local patient populations.17 Using electronic quality measure data, the PCED provides Veterans Integrated Service Network-level and facility-level performance on several metrics.18 The PCED had not been previously used at the CVVAMC, and few publications or quality improvement projects regarding its use have been reported by the VA Office of Health Equity. PCED helped identify disparities when comparing female to male patients in the prescribing of statin therapy for patients with CVD and statin therapy for patients with T2DM.
VA PHASER pharmacogenomic analyses provided an opportunity to expand this quality improvement project. Sanford Health and the VA collaborated on the PHASER program to offer free genetic testing for veterans. The program launched in 2019 and expanded to various VA sites, including CVVAMC in March 2023. This program has been extended to December 31, 2025.
The primary objective of this quality improvement project was to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk. Secondary outcomes included increased pharmacogenomic testing and the assessment of pharmacogenomic results related to statin therapy. This project was approved by the CVVAMC Pharmacy and Therapeutics Committee. The PCED was used to identify female veterans with T2DM and/or CVD without an active prescription for a statin between July and October 2023. A review of Computerized Patient Record System patient charts was completed to screen for prespecified inclusion and exclusion criteria. Veterans were included if they were assigned female at birth, were enrolled in care at CVVAMC, and had a diagnosis of T2DM or CVD (history of myocardial infarction, coronary bypass graft, percutaneous coronary intervention, or other revascularization in any setting).
Veterans were excluded if they were currently pregnant, trying to conceive, breastfeeding, had a T1DM diagnosis, had previously documented hypersensitivity to a statin, active liver failure or decompensated cirrhosis, previously documented statin-associated rhabdomyolysis or autoimmune myopathy, an active prescription for a proprotein convertase subtilisin/kexin type 9 inhibitor, or previously documented statin intolerance (defined as the inability to tolerate ≥ 3 statins, with ≥ 1 prescribed at low intensity or alternate-day dosing). The female veterans were compared to 2 comparators: the facility's male veterans and the VA national average, identified via the PCED.
Once a veteran was screened, they were telephoned between October 2023 and February 2024 and provided education on statin use and pharmacogenomic testing using a standardized note template. An order was placed for participants who provided verbal consent for pharmacogenomic testing. Those who agreed to statin initiation were referred to a clinical pharmacist practitioner (CPP) who contacted them at a later date to prescribe a statin following the recommendations of the 2019 ACC/AHA and 2023 ADA guidelines and pharmacogenomic testing, if applicable.4,5,7 Appropriate monitoring and follow-up occurred at the discretion of each CPP. Data collection included: age, race, diagnoses (T2DM, CVD, or both), baseline lipid panel (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), hepatic function, name and dose of statin, reasons for declining statin therapy, and pharmacogenomic testing results related to SLCO1B1.
Results
At baseline in July 2023, 77.8% of female veterans with T2DM were prescribed a statin, which exceeded the national VA average (77.0%), but was below the rate for male veterans (78.7%) in the facility comparator group.17 Additionally, 82.2% of females with CVD were prescribed a statin, which was below the national VA average of 86.0% and the 84.9% of male veterans in the facility comparator group.17 The PCED identified 189 female veterans from July 2023 to October 2023 who may benefit from statin therapy. Thirty-three females met the exclusion criteria. Of the 156 included veterans, 129 (82.7%) were successfully contacted and 27 (17.3%) could not be reached by telephone after 3 attempts (Figure 1). The 129 female veterans contacted had a mean age of 59 years and the majority were Black (82.9%) (Table 1).
Abbreviations: CVD, cardiovascular disease; PCSK9, proprotein convertase subtilisin/
kexin type 9; T2DM, type 2 diabetes mellitus; VAMC, Veterans Affairs medical center.
Primary Outcomes
Of the 129 contacted veterans, 31 (24.0%) had a non-VA statin prescription, 13 (10.1%) had an active VA statin prescription, and 85 (65.9%) did not have a statin prescription, despite being eligible. Statin adherence was confirmed with participants, and the medication list was updated accordingly.
Of the 85 veterans with no active statin therapy, 37 (43.5%) accepted a new statin prescription and 48 (56.5%) declined. There were various reasons provided for declining statin therapy: 17 participants (35.4%) declined due to concern for AEs (Table 2).
From July 2023 to March 2024, the percentage of female veterans with active statin therapy with T2DM increased from 77.8% to 79.0%. For those with active statin therapy with CVD, usage increased from 82.2% to 90.2%, which exceeded the national VA average and facility male comparator group (Figures 2 and 3).17
Secondary Outcomes
Seventy-one of 129 veterans (55.0%) gave verbal consent, and 47 (66.2%) completed the pharmacogenomic testing; 58 (45.0%) declined. Five veterans (10.6%) had a known SLCO1B1 allele variant present. One veteran required a change in statin therapy based on the results (eAppendix).
Discussion
This project aimed to increase statin prescribing among female veterans with T2DM and/or CVD to reduce cardiovascular risk and increase pharmacogenomic testing using the PCED and care managed by CPPs. The results of this quality improvement project illustrated that both metrics have improved at CVVAMC as a result of the intervention. The results in both metrics now exceed the PCED national VA average, and the CVD metric also exceeds that of the facility male comparator group. While there was only a 1.2% increase from July 2023 to March 2024 for patients with T2DM, there was an 8.0% increase for patients with CVD. Despite standardized education on statin use, more veterans declined therapy than accepted it, mostly due to concern for AEs. Recording the reasons for declining statin therapy offered valuable insight that can be used in additional discussions with veterans and clinicians.
Pharmacogenomics gives clinicians the unique opportunity to take a proactive approach to better predict drug responses, potentially allowing for less trial and error with medications, fewer AEs, greater trust in the clinician, and improved medication adherence. The CPPs incorporated pharmacogenomic testing into their practice, which led to identifying 5 SLCO1B1 gene abnormalities. The PCED served as a powerful tool for advancing equity-focused quality improvement initiatives on a local level and was crucial in prioritizing the detection of veterans potentially receiving suboptimal care.
Limitations
The nature of “cold calls” made it challenging to establish contact for inclusion in this study. An alternative to increase engagement could have been scheduled phone or face-to-face visits. While the use of the PCED was crucial, data did not account for statins listed in the non-VA medication list. All 31 patients with statins prescribed outside the VA had a start date added to provide the most accurate representation of the data moving forward.
Another limitation in this project was its small sample size and population. CVVAMC serves about 6200 female veterans, with roughly 63% identifying as Black. The preponderance of Black individuals (83%) in this project is typical for the female patient population at CVVAMC but may not reflect the demographics of other populations. Other limitations to this project consisted of scheduling conflicts. Appointments for laboratory draws at community-based outpatient clinics were subject to availability, which resulted in some delay in completion of pharmacogenomic testing.
Conclusions
CPPs can help reduce inequity in health care delivery. Increased incorporation of the PCED into regular practice within the VA is recommended to continue addressing sex disparities in statin use, diabetes control, blood pressure management, cancer screenings, and vaccination needs. CVVAMC plans to expand its use through another quality improvement project focused on reducing sex disparities in blood pressure management. Improving educational resources made available to veterans on the importance of statin therapy and potential to mitigate AEs through use of the VA PHASER program also would be helpful. This project successfully improved CVVAMC metrics for female veterans appropriately prescribed statin therapy and increased access to pharmacogenomic testing. Most importantly, it helped close the sex-based gap in CVD risk reduction care.
- Heron M. Deaths: leading causes for 2018. Nat Vital Stat Rep. 2021;70:1-114.
- US Department of Veterans Affairs, US Department of Defense. VA/DoD Clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction. Published June 2020. Accessed August 25, 2025. https://www.healthquality.va.gov/guidelines/CD/lipids/VADODDyslipidemiaCPG5087212020.pdf
- Atherosclerotic Cardiovascular Disease (ASCVD). American Heart Association. Accessed August 26, 2025. https:// www.heart.org/en/professional/quality-improvement/ascvd
- American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S144-S174. doi:10.2337/dc22-S010
- American Diabetes Association. Standards of Care in Diabetes— 2023 abridged for primary care providers. Clinical Diabetes. 2022;41(1):4-31. doi:10.2337/cd23-as01
- Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115:21-26. doi:10.1016/j.amjcard.2014.09.041
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/ AHA Guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
- Buchanan CH, Brown EA, Bishu KG, et al. The magnitude and potential causes of gender disparities in statin therapy in veterans with type 2 diabetes: a 10-year nationwide longitudinal cohort study. Womens Health Issues. 2022;32:274-283. doi:10.1016/j.whi.2021.10.003
- Ahmed F, Lin J, Ahmed T, et al. Health disparities: statin prescribing patterns among patients with diabetes in a family medicine clinic. Health Equity. 2022;6:291-297. doi:10.1089/heq.2021.0144
- Metser G, Bradley C, Moise N, Liyanage-Don N, Kronish I, Ye S. Gaps and disparities in primary prevention statin prescription during outpatient care. Am J Cardiol. 2021;161:36-41. doi:10.1016/j.amjcard.2021.08.070
- Nanna MG, Wang TY, Xiang Q, et al. Sex differences in the use of statins in community practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562. doi:10.1161/CIRCOUTCOMES.118.005562
- Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016;9:97-106. doi:10.2147/PGPM.S86013
- Türkmen D, Masoli JAH, Kuo CL, Bowden J, Melzer D, Pilling LC. Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men. Br J Clin Pharmacol. 2022;88:3230-3240. doi:10.1111/bcp.15245
- Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111:1007-1021. doi:10.1002/cpt.2557
- Ramsey LB, Gong L, Lee SB, et al. PharmVar GeneFocus: SLCO1B1. Clin Pharmacol Ther. 2023;113:782-793. doi:10.1002/cpt.2705
- National Healthcare Quality and Disparities Report: Chartbook on Healthcare for Veterans. Rockville (MD): Agency for Healthcare Research and Quality (US); November 2020.
- Procario G. Primary Care Equity Dashboard [database online]. Power Bi. 2023. Accessed August 26, 2025. https://app.powerbigov.us
- Hausmann LRM, Lamorte C, Estock JL. Understanding the context for incorporating equity into quality improvement throughout a national health care system. Health Equity. 2023;7(1):312-320. doi:10.1089/heq.2023.0009
- Heron M. Deaths: leading causes for 2018. Nat Vital Stat Rep. 2021;70:1-114.
- US Department of Veterans Affairs, US Department of Defense. VA/DoD Clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction. Published June 2020. Accessed August 25, 2025. https://www.healthquality.va.gov/guidelines/CD/lipids/VADODDyslipidemiaCPG5087212020.pdf
- Atherosclerotic Cardiovascular Disease (ASCVD). American Heart Association. Accessed August 26, 2025. https:// www.heart.org/en/professional/quality-improvement/ascvd
- American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S144-S174. doi:10.2337/dc22-S010
- American Diabetes Association. Standards of Care in Diabetes— 2023 abridged for primary care providers. Clinical Diabetes. 2022;41(1):4-31. doi:10.2337/cd23-as01
- Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115:21-26. doi:10.1016/j.amjcard.2014.09.041
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/ AHA Guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
- Buchanan CH, Brown EA, Bishu KG, et al. The magnitude and potential causes of gender disparities in statin therapy in veterans with type 2 diabetes: a 10-year nationwide longitudinal cohort study. Womens Health Issues. 2022;32:274-283. doi:10.1016/j.whi.2021.10.003
- Ahmed F, Lin J, Ahmed T, et al. Health disparities: statin prescribing patterns among patients with diabetes in a family medicine clinic. Health Equity. 2022;6:291-297. doi:10.1089/heq.2021.0144
- Metser G, Bradley C, Moise N, Liyanage-Don N, Kronish I, Ye S. Gaps and disparities in primary prevention statin prescription during outpatient care. Am J Cardiol. 2021;161:36-41. doi:10.1016/j.amjcard.2021.08.070
- Nanna MG, Wang TY, Xiang Q, et al. Sex differences in the use of statins in community practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562. doi:10.1161/CIRCOUTCOMES.118.005562
- Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016;9:97-106. doi:10.2147/PGPM.S86013
- Türkmen D, Masoli JAH, Kuo CL, Bowden J, Melzer D, Pilling LC. Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men. Br J Clin Pharmacol. 2022;88:3230-3240. doi:10.1111/bcp.15245
- Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111:1007-1021. doi:10.1002/cpt.2557
- Ramsey LB, Gong L, Lee SB, et al. PharmVar GeneFocus: SLCO1B1. Clin Pharmacol Ther. 2023;113:782-793. doi:10.1002/cpt.2705
- National Healthcare Quality and Disparities Report: Chartbook on Healthcare for Veterans. Rockville (MD): Agency for Healthcare Research and Quality (US); November 2020.
- Procario G. Primary Care Equity Dashboard [database online]. Power Bi. 2023. Accessed August 26, 2025. https://app.powerbigov.us
- Hausmann LRM, Lamorte C, Estock JL. Understanding the context for incorporating equity into quality improvement throughout a national health care system. Health Equity. 2023;7(1):312-320. doi:10.1089/heq.2023.0009
Reducing Sex Disparities in Statin Therapy Among Female Veterans With Type 2 Diabetes and/or Cardiovascular Disease
Reducing Sex Disparities in Statin Therapy Among Female Veterans With Type 2 Diabetes and/or Cardiovascular Disease