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RCT on PGx-Guided Clopidogrel Therapy

This document discusses the debate around implementing a randomized controlled trial (RCT) to examine pharmacogenetics (PGx)-guided clopidogrel therapy. Some argue an RCT is needed for guidelines to endorse PGx recommendations, while others argue it would be unethical since current studies show 18-45% of patients are poor metabolizers and at high risk of adverse events without PGx testing. The document also provides background on PGx variations affecting clopidogrel metabolism and existing guidelines on dosing.

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Michelle Kristine Donnelly
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68 views1 page

RCT on PGx-Guided Clopidogrel Therapy

This document discusses the debate around implementing a randomized controlled trial (RCT) to examine pharmacogenetics (PGx)-guided clopidogrel therapy. Some argue an RCT is needed for guidelines to endorse PGx recommendations, while others argue it would be unethical since current studies show 18-45% of patients are poor metabolizers and at high risk of adverse events without PGx testing. The document also provides background on PGx variations affecting clopidogrel metabolism and existing guidelines on dosing.

Uploaded by

Michelle Kristine Donnelly
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as DOCX, PDF, TXT or read online on Scribd
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RCT examining PGx-Guided Clopidogrel Therapy Debate

Clopidogrel in pts with ACS undergoing PCI, ASC has stated that they will not endorse these recommendations
unless a large randomized control trial RCT is run. PGx experts have stated that they consider this unethical.
Background on relationship between pharmacogenetic gene variants and clopidogrel dosing recommendations:
Prasugrel, ticagrelor, etc.  ischemic events, etc. more than clopidogrel but also higher bleeding. Does not hold its own
compared to others in its class. AE: Bleeding, rash, dyspepsia, abdominal pain, diarrhea. BUT ODB, Generic available. Po
qd.
PGx Variation: 2C19 Highly polymorphic, > 25 known variants. *1 wild, *2 most common loss of func. 3-8 =
reduced/absent enzymatic activity *2 allele freq 12-15% cauc & afri, 29-35% Asian.

CPIC/Dutch WG Guidelines: IM (18-455) Reduced plt inhibition, increased CV events. PM too (2-15%) DO NOT USE
CLOPIDOGREL. Label-recommended dosage for UM (gain of function, *17) or EM.

Implement an RCT examining PGx-guided Informed Do not implement an RCT examining PGx-guided vs
therapy with Clopidogrel (PRO) non-PGx informed therapy w/clopidogrel
1. RCT will better inform guidelines which will 1. Guidelines for ACS (and other clop
translate to increase ther and safety outcomes indications) already exist. CCV switching to
2. Cost-effective to use PGx testing, QoL. Ticagrelor over Clopidogrel anyway.
Long term may be more expensive with 2. Other study designs have been completed to
clopidogrel if paying for complications of support the use of PGx testing.
ineffective therapy (thrombosis, vte, etc). 3. Ethical consideration: It is unethical to run an
Give ticagrelor to those with loss of function RCT (one arm with PGx testing, one arm
allele b/c though more expensive it’s cost- without PGx testing) knowing that pts without
effective compared to ineffective drug. PGx testing are at high risk of AEs. We know
3. Current studies underway to show that 18-45% are PM and 8-10% are IM,
effectiveness of Pgx Testing unethical to give them standard therapy. 20-
4. American society of cardiology will only 30% with ACS had inadequate response to
endorse pGx recommendations if an RCT has clop, even 1 polymorphic allele seems to have
been done. 2 insurance companies cover, 4 an effect.
don’t b/c of it. In 2014 Coverage w/evidence 4. Better implementation of guidelines needed
development needed for medicare. before changing them. Educate prescribers,
5. More optimal dose needed for what to do with RPh, etc.
data whether increase dose, etc. than just 5. Unrealistic to do an RCT on every drug that
switch. can use PGx testing, better to just focus on
6. Non-RCT trials are not preferable. implementation and make that easier/more
7. The vast majority does not have access to PGx cost-effective.
testing, so that is the standard of care, whether 6. 21.5% had major major AE in response to no
unethical or not. response from IM. EM it was 13%.
8. TAILOR-pci 2019. Using ticagrelor as
standard of care overcomes ethical issues –
but still no direct comparison of clop with or
without PGx testing. POPular Completion
March 2020.

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