Cost Avoidance with

Preemptive CYP2C19
Genotype Testing Prior to
Clopidogrel Initiation Post
Percutaneous Coronary
Intervention
Sydney M. Stratford, PharmD, MS PGx, BS
PGY1 Acute Care Pharmacy Resident
Saint Joseph Health System, Mishawaka, IN
Lisa J. Ribble-Fay, PharmD, BS, BCPS
Acute Care Residency Director, Clinical Coordinator
Saint Joseph Health System, Mishawaka, IN

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 Disclosure Statement
The speaker and preceptor mentor have no actual or potential
conflicts of interest in relation to this presentation.

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Purpose

Quantify patients readmitted for a major adverse cardiovascular event (MACE) or

hemorrhage after being given clopidogrel, post-percutaneous coronary intervention (PCI).

Compare and contrast hospital costs associated with MACE/hemorrhage events to

cost of CYP2C19 genotype testing.

Determine cost avoidance with preemptive CYP2C19 testing.

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 1,2
Background
FDA approved indications:
• ACS, Recent MI or stroke, established
PAD
Boxed Warning (package insert):
• “Diminished Antiplatelet Effect in
Patients with Two Loss-Of-Function
Alleles of CYP2C19 Gene”

CYP2C19
Genotype Results

UM (*1/*17) RM (*1/*1) IM (*1/*2) PM (*2/*2)

Image courtesy of: https://www.pharmgkb.org/pathway/PA154424674

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Self-Assessment Question

Clopidogrel has an FDA-approved indication for which of the

following:
A. Stable ischemic heart disease
B. ST-elevation myocardial infarction
C. Coronary artery bypass graft surgery
D. Percutaneous coronary intervention for stable ischemic heart
disease

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Self-Assessment Question

Which of the following genotypes would result in a poor

metabolizer phenotype?
A. *1/*17
B. *1/*2
C. *2/*2
D. *1/*1

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 3
Background cont. | TAILOR-PCI
Objective
Post hoc analysis: 79% reduction in adverse events in the first 3 months in the genotype-guided
• group compared
Determine effectwith those in the standard
of genotype-guided oraltherapy
P2Y12group; maystrategy
inhibitor indicate on
a particularly high-risk in
ischemic outcomes
CYP2C19 LOF carriers after PCI window of time after stenting
Intervention
Pre-specified analysis demonstrated 39% (p=0.01) reduction in cumulative or multiple ischemic
• Patients randomizedevents
to genotype-guided
per patient withgroup underwent therapy.
genotype-guided POC genotyping.
• CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel.
• Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and
"Although these results fell short of the effect size that we predicted, they nevertheless provide a
underwent genotyping after 12 months
signal that offers support for the benefit of genetically guided therapy, with approximately one-third
Results
fewer adverse events in the patients who received genetically guided treatment compared with those
• Composite endpoint occurred in 3.9%who did not,“
(35/903) of the genotype-guided group, and in 5.7%
-Naveen
(54/946)L.ofPereira, M.D., cardiologist
the standard at Mayo
therapy group (p =Clinic in Rochester, Minnesota, and co-principal
0.056).
investigator of the study
• Genotype-guided strategy yielded a 34% reduction in cardiovascular events but did not
reach the 50% reduction target.
Pereira NL, Farkouh ME, So D, Lennon R, et al. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional
Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized
Clinical Trial. JAMA. 2020 Aug 25;324(8):761-771. doi: 10.1001/jama.2020.12443. PMID: 32840598; PMCID: PMC7448831 7
©2014 Trinity Health. All Rights Reserved.
Methods
• Retrospective, observational, Clopidogrel
case-series study and PCI
• January 1, 2019, through June
30, 2021 MACE Hemorrhage
events events
Major Adverse Cardiovascular Events
Myocardial infarction Stable angina
STEMI Atypical chest pain Hemorrhage Events
NSTEMI Cardiogenic shock
Intracranial Anemia
Unstable angina Stroke
Ischemic stroke Heart failure Intracerebral Other bleeding

Unspecified stroke CABG Other intracerebral Gastrointestinal

PCI Subarachnoid

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Methods cont.

Baseline Adverse ICD-10 Associated

population effects code DRG cost

CYP2C19 Population Cost

Lab cost frequency comparison

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Results
Total Patients: 5,492 Event Rate Occurrence
Total Events: 6,170 6000 5,496
White 5000
Black
Asian 4000
88%
Other
3000

IM and PM Phenotype Frequency in American 2000

Population:
0.2138 + 0.0148 = 22.9%
1000
674
UM and RM Phenotype Frequency in American
0
Population:
0.0074 + 0.1364 = 14.4% MACE Hemorrhage

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Results cont.
Total Events Est. price Population Adjusted Adjusted
MACE and Hemorrhage (MACE) per event frequency total events total cost
Total US Dollar Cost (Mil-
lions) 5,496 $10,012 22.9% 1,258 $12,595,096
60000000 55

50000000
CYP2C19 cost Total patients Total CYP2C19 cost
40000000
$400 5,492 $2,196,800
30000000

20000000

10000000
3.1 Cost Avoidance MACE:
0
$10,398,296
MACE Hemorrhage

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Results cont.
Est. price Population Adjusted Adjusted
MACE and Hemorrhage Total Events
per event frequency total events total cost
Total US Dollar Cost (Mil-
lions) 674 $4,689 14.4% 97 $454,833
60000000 55

50000000
CYP2C19 cost Total patients Total CYP2C19 cost
40000000
$400 5,492 $2,196,800
30000000

20000000

10000000
3.1 Cost Avoidance Hemorrhage:
0
-$1,741,967
MACE Hemorrhage

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 Strengths

• One-of-a-kind study
• Provides evidence that there may be
benefits to preemptive testing

Strengths and Limitations

Limitations • Retrospective
• EMR data gathering
• Many ICD-10 codes per DRG cost
• Dependent on DRG code billing
• Average cost per event
• Population percentages

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Conclusion and Discussion

• Results found provide compelling evidence for cost avoidance

with preemptive CYP2C19 genotype testing.

• Need for more robust studies in this area to confidently conclude

that preemptive CYP2C19 testing will provide a cost avoidance
to healthcare institutions.

• Future studies could alter prescribing and workflow processes.

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Questions?

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 Thank you!

Sydney M. Stratford, PharmD, MS PGx, BS

PGY1 Acute Care Pharmacy Resident
Saint Joseph Health System, Mishawaka, IN
Sydney.Stratford001@sjrmc.com

©2014 Trinity Health. All Rights Reserved. 16

References
1. ACI Healthcare USA, Inc. Clopidogrel bisulfate tablet, film coated. Updated 2020 June; cited
2022 April. In: DailyMed (Internet). Bethesda (MD): National Library of Medicine (US).
Available from:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52902cfe-2863-490a-b700-3f47df
e3cf50
.
2. Clinical Pharmacogenomics Implementation Consortium (CPIC). Update 2021 October;
cited 2022 April. Available from: https://cpicpgx.org/.
3. Pereira NL, Farkouh ME, So D, Lennon R, et al. Effect of Genotype-Guided Oral P2Y12
Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After
Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA.
2020 Aug 25;324(8):761-771. doi: 10.1001/jama.2020.12443. PMID: 32840598; PMCID:
PMC7448831.

©2014 Trinity Health. All Rights Reserved. 17