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Programs Program for Personalized and Genomic MedicineFor Healthcare ProvidersTreatment Recommendations

Treatment Recommendations

Treatment Recommendations for Patients with Acute Coronary Syndromes (ACS) or Percutaneous Coronary Intervention (PCI) Requiring Long-term Dual Anti-Platelet Therapy Based on CYP2C19 Genotype

Recommendations based upon guidelines published by the Clincial Pharmacogenetics Implementation Consortium (CPIC)1.

Genotype Treatment Recommendations
Normal Metabolizer
*1/*1 • Clopidogrel (PLAVIX) 75 mg daily
Intermediate Metabolizers
*1/*2

• Ticagrelor (BRILINTA) 180 mg loading dose followed by 90 mg twice daily
*Contraindications: History of intracranial hemorrhage, active bleeding
*Caution: Aspirin dose > 100 mg/day reduces ticagrelor effectiveness and should be avoided

OR

• Prasugrel (EFFIENT) 60 mg loading dose followed by 10 mg daily
*Contraindications: History of stroke or transient ischemic attack, active bleeding
*Caution: Increased bleeding risk: Age > 75 years, body weight < 60 kg
*Prasugrel 5 mg may be considered for patients < 60 kg however the effectiveness and safety of this dose has not been prospectively studied in this group of patients

OR

• if neither of these is appropriate consider INCREASED DOSE of clopidogrel (PLAVIX) to 225 mg daily†
*1/*3
*1/*4
*1/*6
*1/*8
*2/*17
*3/*17
*4/*17
*6/*17
*8/*17
Poor Metabolizers
*2/*2
• Ticagrelor (BRILINTA) 180 mg loading dose followed by 90 mg twice daily 
*Contraindications: History of intracranial hemorrhage, active bleeding
*Caution: Aspirin dose > 100 mg/day reduces ticagrelor effectiveness and should be avoided

OR

• Prasugrel (EFFIENT) 60 mg loading dose followed by 10 mg daily.
*Contraindications: History of stroke or transient ischemic attack, active bleeding
*Caution: Increased bleeding risk: Age >75 years, body weight < 60 kg
* Prasugrel 5 mg may be considered for patients < 60 kg however the effectiveness and safety of this dose has not been prospectively studied in this group of patients
*2/*3
*2/*4
*2/*6
*2/*8
*3/*3
*3/*4
*3/*6
*3/*8
*4/*4
*4/*6
*4/*8
*6/*6
*6/*8
*8/*8
Rapid Metabolizers††
 
*1/*17
• Clopidogrel (PLAVIX) 75 mg daily††
Ultra-Rapid Metabolizers††
 
*17/*17
• Clopidogrel (PLAVIX) 75 mg daily††

†The increased dose has efficacy on platelet reactivity/pharmacokinetics in Intermediate Metabolizers similar to 75 mg daily in normal metabolizers, but does not have patient outcome data available. While not supported by the 2013 CPIC guidelines, this dosage is approved as a second-line therapy (when prasugrel or ticagrelor are not appropriate) by the UMMC P&T Committee’s Pharmacogenomics Subcommittee based upon platelet reactivity and pharmacokinetic data.1-10.

†† Rapid and Ultra-rapid metabolizers may be at increased risk of bleeding complications.

References:

  1. Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther 2013;94:317-23.
  2. Gladding P, Webster M, Zeng I, et al. The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial. JACC Cardiovasc Interv 2008;1:620-7.
  3. Gladding P, White H, Voss J, et al. Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: a dose-escalation study. JACC Cardiovasc Interv 2 009;2:1095-101.
  4. Barker CM, Murray SS, Teirstein PS, Kandzari DE, Topol EJ, Price MJ. Pilot study of the antiplatelet effect of increased clopidogrel maintenance dosing and its relationship to CYP2C19 genotype in patients with high on-treatment reactivity. JACC Cardiovasc Interv 2010;3:1001-7.
  5. Bonello L, Armero S, Ait Mokhtar O, et al. Clopidogrel loading dose adjustment according to platelet reactivity monitoring in patients carrying the 2C19*2 loss of function polymorphism. J Am Coll Cardiol 2010;56:1630-6.
  6. Alexopoulos D, Panagiotou A, Xanthopoulou I, et al. Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity. J Thromb Haemost 2011;9:2379-85.
  7. Collet JP, Hulot JS, Anzaha G, et al. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study 2). JACC Cardiovasc Interv 2011;4:392-402.
  8. Cuisset T, Quilici J, Cohen W, et al. Usefulness of high clopidogrel maintenance dose according to CYP2C19 genotypes in clopidogrel low responders undergoing coronary stenting for non ST elevation acute coronary syndrome. Am J Cardiol 2011;108:760-5.
  9. Horenstein RB, Madabushi R, Zineh I, et al. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers. J Clin Pharmacol 2014;54:865-73.
  10. Cavallari LH, Lee CR, Beitelshees AL, et al. Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2017 Oct 25. pii: S1936-8798(17)31499-1.

Pharmacogenetics Service & Contacts:

Pharmacogenetics Service Team:

  • Amber Beitelshees, PharmD, MPH: 410-706-0118
  • Linda Jeng, MD, PhD, FACMG: 440-554-5859
  • Kristin Maloney, MS, MGC, CGC: 410-706-6071
  • Mark Vesely, MD: 410-746-9423

For General Questions:

PPGM clinical research office 410-706-6140
Email address: ppgm@medicine.umaryland.edu

The UMMC Pharmacogenetics Subcommittee of the Pharmacy & Therapeutics Committee and the Translational Genomics Laboratory are responsible for the content of the page.