Integrating Pharmacogenetics In Clinical Care

Variants at rs4149056 in the SLCO1B1 gene are associated with a greater risk of
simvastatin-related myopathy. Despite the growing implementation of SLCO1B1 rs4149056
genotyping in health systems across the United States, there is little randomized controlled
trial data on the impact of SLCO1B1 testing on clinical outcomes. The IPICC Study will use a
randomized design to determine the impact of the clinical integration of SLCO1B1 genotype
testing on important patient outcomes, including statin prescribing, LDL cholesterol, and
statin-related myopathy. In addition, by enrolling statin-naive patients with a recent
cholesterol panel, this trial will capture a moment of clinical decision-making when SLCO1B1
rs4149056 genotype might be most clinically relevant. This randomized-control trial has two
primary aims:

Aim 1 (Drug safety): To determine the impact of SLCO1B1 pharmacogenetic testing on
concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) pharmacogenetic
guidelines for safe simvastatin prescribing and on the incidence of statin-related myopathy
in VA (drug safety).

Aim 2 (Cardiovascular disease, CVD, prevention): To determine the impact of SLCO1B1
pharmacogenetic testing on LDL cholesterol levels and concordance with CVD prevention
guidelines.

The I-PICC Study is enrolling 408 statin-naive primary care and women's health patients
across the Veteran Affairs Boston Healthcare System. Eligible patients are aged 40-75 and
have elevated risk of cardiovascular disease (CVD) according to American College of
Cardiology/American Heart Association (ACC/AHA) guidelines. Primary care providers (PCPs) are
also research subjects and consent via electronic health record (EHR) alerts. To model
pharmacogenotyping at the point of care, the investigators are enrolling patients with recent
cholesterol results when their PCPs order laboratory testing, indicating a moment of clinical
decision-making about CVD risk. Enrolled patients are randomized to have their PCPs receive
results through the EHR immediately (PGx+) vs. after 1 year (PGx-). The investigators will
query clinical and pharmacy data for 1-year outcomes: myopathy and concordance with CPIC
simvastatin guidelines (drug safety) and cholesterol levels and concordance with ACC/AHA
guidelines (CVD risk reduction).

Inclusion Criteria:

Providers:

- All providers in Primary Care and Women's Health at VA Boston Healthcare System will
be eligible to participate.

Patients:

- Aged 40-75 years

- Have no history of statin use

- Have received VA care for at least the prior 6 months

- Are a patient of an enrolled provider

- Meet at least 1 of the following criteria:

- cardiovascular disease (CVD)

- diabetes

- LDL cholesterol value >= 190 mg/dL

- 10-year CVD risk of 7.5%, calculated with the ACC/AHA 2013 pooled risk equations

Exclusion Criteria:

- Patients will be ineligible if they:

- Do not meet the inclusion criteria

- Pregnant

- Incarcerated or institutionalized