Pharmacogenomic Informed Statin Prescribing

NCT ID: NCT06568601

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2028-07-28

Brief Summary

Statins are the most cost-effective medications to lower cholesterol and cardiovascular disease (CVD) risk. However, many patients at high-risk for CVD do not accept or adhere to statins. This gap in patient's use of statins limits the full impact of these effective medications resulting in higher cholesterol levels and CVD risk. The main barriers to using statins are patients' perceived lack of benefit, excess risk of statin toxicity as well as their misperceptions of their CVD risk. Statin pharmacogenomic testing - an application of precision medicine - is a readily available, feasible, and inexpensive intervention that addresses this barrier by using genetic testing to identify the nearly 1 out of 2 patients with enhanced benefit and/or reduced risk of statin toxicity or increased risk for CVD. By communicating statin pharmacogenomic test results to Veterans at high-risk for CVD not taking statin therapy, the investigators aim to improve patients' perceptions of their risk of CVD and statins and, in turn, their acceptance of and adherence to statins to reduce their cholesterol levels and CVD risk.

Detailed Description

Background: Despite the proven efficacy and safety of statins, nearly 250,000 Veterans at high-risk for cardiovascular disease (CVD) seen annually in primary care are not taking them leading to higher cholesterol levels, cardiovascular risk, and health care costs. Primary care providers and health systems have a critical and unmet need for pragmatic, scalable interventions to address gaps in their patients' perceptions of the risks and benefits of statin therapy to improve appropriate statin utilization and to lower CVD risk. Important prior work by the investigators group demonstrates that pharmacogenomic testing for statin toxicity is feasible, improves patients' perceptions of statin therapy, leads to a doubling in appropriate statin prescribing, and lowers cholesterol levels. The central hypothesis of this proposal is that disclosure of statin pharmacogenomic test results for statin efficacy/toxicity and CVD risk to patients at high-risk for CVD will improve their perceptions of their CVD risk and statins risks/benefits and, in turn, the proportion of Veterans accepting and adhering to statin therapy to achieve a clinically significant low-density lipoprotein cholesterol (LDL) reduction.

Significance: By using a feasible and inexpensive approach of pharmacogenomic testing for common genetic variants reporting on statin efficacy and toxicity and CVD risk, the work is significant as it will lead to more patients at high-risk for CVD accepting and adhering to statins. This work addresses HSR&D research priorities of quality and safety of health care and health care value, ORD priorities of increasing substantial real-world impact of VA research, and VHA quality measures around statin prescribing and controlling cholesterol levels in patients at high-risk for CVD.

Innovation and Impact: This proposal uses an innovative approach of pharmacogenomic testing to address patients' perceptions of the risks and benefits of statin therapy and their risk of CVD which are known barriers to statin acceptance and adherence. The investigators expect a positive impact on reducing CVD risk in Veterans.

Specific Aims:

1. Reduce cholesterol levels through a precision medicine approach of statin pharmacogenomic testing.

2. Improve acceptance of guideline-directed statin therapy through delivery of statin pharmacogenomic test results that communicates statin efficacy and toxicity.

3. Identify contextual and economic factors salient for implementing statin pharmacogenomic testing.

Methodology: A randomized controlled trial focused on effectiveness while secondarily gathering implementation data will enroll 408 primary care patients who are at high-risk for CVD and recommended for statins based on guidelines but not prescribed them. Participants will be randomized 1:1 to intervention (guideline-based statin recommendations - "guidelines" - plus statin pharmacogenomic test results) vs. control (guidelines) stratified by prior statin use. The primary outcome is change in 12-month LDL. Secondary outcomes are new statin prescriptions and patients' perceptions of risks and benefits of statins. Exploratory analyses will assess statin prescriptions and fills as potential mediators of the intervention. Qualitative data from trial participants and their providers will illuminate key factors to consider for future implementation. If effective, the cost-effectiveness and budget impact of the intervention on LDL during the trial period projected over 10-year and lifetime CVD risk horizons will be measured.

Next steps/Implementation: An embedded primary care, patient-powered caucus and a VA operational stakeholder board representing primary care, cardiology, pharmacy, and the VA Pharmacogenomics Testing for Veterans (PHASER) clinical program will work with the investigative team to create an implementation "blueprint" package consisting of patient/provider educational portfolios, electronic medical record tools, Corporate Data Warehouse queries, and laboratory protocols for dissemination to Veterans and VHA facilities.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Genetic testing arm

The intervention involves: genetic testing; interpretation; and prior to and shortly following an upcoming appointment, communication to patients and providers about the patients' predicted statin efficacy and toxicity, genetic risk for CVD, and individualized recommended statin type/dose.

Group Type: EXPERIMENTAL

Pharmacogenetic and polygenic risk testing

Intervention Type: GENETIC

The intervention involves: genetic testing; interpretation; and prior to and shortly following an upcoming appointment, communication to patients and providers about the patients' predicted statin efficacy and toxicity, genetic risk for CVD, and individualized recommended statin type/dose.

Control

The control condition involves receipt of a report highlighting the risk of cardiovascular disease and benefits of statins (without genetic test results).

Group Type: ACTIVE_COMPARATOR

Active control

Intervention Type: OTHER

The control condition involves receipt of a report highlighting the risk of cardiovascular disease and benefits of statins (without genetic test

Interventions

Pharmacogenetic and polygenic risk testing

The intervention involves: genetic testing; interpretation; and prior to and shortly following an upcoming appointment, communication to patients and providers about the patients' predicted statin efficacy and toxicity, genetic risk for CVD, and individualized recommended statin type/dose.

Intervention Type: GENETIC

Active control

The control condition involves receipt of a report highlighting the risk of cardiovascular disease and benefits of statins (without genetic test

Intervention Type: OTHER

Other Intervention Names

Control

Eligibility Criteria

Inclusion Criteria

Patients will be included in the analysis if they:

• Are a Veteran
• Aged 40-75 years
• Diabetes mellitus or cardiovascular disease (coronary, cerebral, or peripheral artery disease)
• An upcoming primary care appointment in the next 4 months
• No active statin prescription (any time/dose, VA, or non-VA) in the prior 6 months
• English speaking
• At least 1 current active VA prescription
• At least 1 primary care appointment within the prior 2 years

Exclusion Criteria

• Non-Veterans
• End-stage renal disease
• History of rhabdomyolysis
• Active treatment for non-dermatologic cancer
• Known, prior SLCO1B1 genetic test results
• Liver cirrhosis
• Palliative care or hospice in 1-year prior to admission, during hospital stay, or at discharge
• Active prescription for PCSK9 inhibitor
• Inability to provide informed consent due to language impairment, cognitive disease, or other similar factors at the discretion of the research assistant or project coordinator.
• Active enrollment in a different, interventional clinical trial, at the discretion of PI.
• History of allogeneic stem cell transplant or liver transplant.
• Documentation of specific adverse drug reactions thought to be attributed to statins:

• Myopathy with associated elevation in creatinine kinase > 10x upper limit of normal
• Angioedema
• Elevated AST/ALT
• Others at discretion of PI

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deepak Voora, MD

Role: PRINCIPAL_INVESTIGATOR

Durham VA Medical Center, Durham, NC

Dawn M. Bravata, MD

Role: PRINCIPAL_INVESTIGATOR

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Locations

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States

Site Status: RECRUITING

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Deepak Voora, MD

Role: CONTACT

deepak.voora@va.gov

(919) 286-0411 ext. 175214

Facility Contacts

Dawn M Bravata, MD

Role: primary

Dawn.Bravata2@va.gov

317-988-2676

Ali E Sexson, BS MBA

Role: backup

ali.sexson@va.gov

Deepak Voora, MD

Role: primary

deepak.voora@va.gov

919-286-0411 ext. 175214

Other Identifiers

I01HX003477-01A3

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IIR 21-040

Identifier Type: -

Identifier Source: org_study_id