Projected impact of genotype-guided optimization of medication use: evidence for preemptive genotyping in cardiac catheterization laboratory patients
Creators: name: Li, Amy
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: Background: Preemptive genotyping is a strategy that tests for multiple pharmacogenomic variants
before a drug is prescribed. Pharmacogenomic information currently appears in 165 FDA-approved drug
labels, and many medications have FDA boxed warnings and/or available Clinical Pharmacogenetics
Implementation Consortium (CPIC) guidelines that recommend action, such as selecting a different drug
or dose, in patients with certain genotypes if the genetic test result was available. However, the
implementation of established pharmacogenomic guidance is hardly done in clinical practice due to the
lack of a clear population to genotype. Cardiac catheterization laboratory patients serve as a reasonable
population due to their multiple comorbidities and increased likelihood of being on genetically
actionable drugs. The objective of this study was to retrospectively assess the projected number of
actionable pharmacogenetic-guided interventions that could have resulted with preemptive genotyping
within a six-month time period for cardiac catheterization laboratory patients.
Methods: This single-center, retrospective study of an established cohort included 183 patients referred
for coronary angiography between September 2012 and February 2014 at UNC Hospitals. A list of 20
drugs with genetically actionable FDA boxed warnings and/or CPIC guidelines was established a priori to
guide medication collection. For these drugs, the relevant genes are HLA-B, CYP2C19, CYP2D6, CYP2C9,
SLCO1B1, VKORC1/CYP2C9, and DYPD. Medication information was collected at discharge and at first
follow-up. The primary endpoint was the projected number of genotype-guided interventions at
discharge or first follow-up that could have occurred using published allele frequencies to estimate the
projected presence of at-risk genotypes. Secondary endpoints included the distribution of total
interventions by gene in the study population, and the projected annual number of genotype-guided
interventions at discharge or first follow-up in the UNC catheterization laboratory patient population.
Results: The study population included 122 patients who had a first follow-up visit within 180 days of the
catheterization. Patients were on average 63 years old, 57% male, and 73% Caucasian. Comorbidities
included depression (13.9%), hyperlipidemia (63.9%), and heart failure (17.2%). Approximately 38% of
patients underwent a percutaneous coronary intervention during the catheterization procedure. The
most prevalent genetically actionable drugs at discharge or first follow-up were clopidogrel (48.4%),
antidepressants (20.5%), simvastatin (13.9%), and warfarin (9.0%). Corresponding at risk genotypes of
interest and projected frequencies were CYP2C19 intermediate or poor metabolizers (28.9%) for
clopidogrel, CYP2C19 ultra-rapid or poor metabolizers (32.5%) for antidepressants, SLCO1B1 C allele
carriers (23.6%) for simvastatin, and VKORC1/CYP2C9 sensitive or highly sensitive responders (38.3%) for
warfarin. The total projected number of genotype-guided interventions at discharge or first follow-up in
the study population was 32. Distribution of total interventions by gene was as follows: 71.9% CYP2C19,
12.5% SLCO1B1, 12.5% VKORC1/CYP2C9, and 3.1% CYP2C9. Assuming each intervention is unique to one
patient, a genotype-guided medication intervention could have been made in 26.2% (32 of 122) of the
study population within 6 months of their presentation to the cardiac catheterization laboratory. When
carried out to the annual UNC Catheterization Laboratory population, the total projected number of
genotype-guided interventions at discharge or first follow-up increased to 565.
Conclusions: A preemptive genotyping strategy with a multi-gene panel in cardiac catheterization
laboratory patients would result in genotype-guided interventions in approximately 1 out of every 4
patients. Almost 30% of interventions involved non-CYP2C19 drugs, suggesting the potential benefit of a
multiplexed genotyping approach that extends beyond CYP2C19 testing.