Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

Larisa H. Cavallari, Craig R. Lee, Amber L. Beitelshees, Rhonda M. Cooper-DeHoff, Julio D. Duarte, Deepak Voora, Stephen E. Kimmel, Caitrin W. McDonough, Yan Gong, Chintan V. Dave, Victoria M. Pratt, Tameka D. Alestock, R. David Anderson, Jorge Alsip, Amer K. Ardati, Brigitta C. Brott, Lawrence Brown, Supatat Chumnumwat, Michael J. Clare-Salzler, James C. CoonsJoshua C. Denny, Chrisly Dillon, Amanda R. Elsey, Issam S. Hamadeh, Shuko Harada, William B. Hillegass, Lindsay Hines, Richard B. Horenstein, Lucius A. Howell, Linda J.B. Jeng, Mark D. Kelemen, Y. M. Lee, Oyunbileg Magvanjav, May Montasser, David R. Nelson, Edith A. Nutescu, Devon C. Nwaba, Ruth E. Pakyz, Kathleen Palmer, Josh F. Peterson, Toni I. Pollin, Alison H. Quinn, Shawn W. Robinson, Jamie Schub, Todd Skaar, D. Max Smith, Vindhya B. Sriramoju, Petr Starostik, Tomasz P. Stys, James M. Stevenson, Nicholas Varunok, Mark R. Vesely, Dyson T. Wake, Karen E. Weck, Kristin W. Weitzel, Russell A. Wilke, James Willig, Richard Y. Zhao, Rolf Kreutz, George A. Stouffer, Philip E. Empey, Nita A. Limdi, Alan R. Shuldiner, Almut G. Winterstein, Julie A. Johnson

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Original languageEnglish (US)
JournalJACC: Cardiovascular Interventions
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Percutaneous Coronary Intervention
clopidogrel
Alleles
Genotype
Complementary Therapies
Therapeutics
Confidence Intervals
Cytochrome P-450 CYP2C19
Acute Coronary Syndrome
Stroke
Myocardial Infarction
Weights and Measures

Keywords

  • Antiplatelet therapy
  • Cardiovascular events
  • Clopidogrel
  • CYP2C19
  • Percutaneous coronary intervention
  • Pharmacogenomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. / Cavallari, Larisa H.; Lee, Craig R.; Beitelshees, Amber L.; Cooper-DeHoff, Rhonda M.; Duarte, Julio D.; Voora, Deepak; Kimmel, Stephen E.; McDonough, Caitrin W.; Gong, Yan; Dave, Chintan V.; Pratt, Victoria M.; Alestock, Tameka D.; Anderson, R. David; Alsip, Jorge; Ardati, Amer K.; Brott, Brigitta C.; Brown, Lawrence; Chumnumwat, Supatat; Clare-Salzler, Michael J.; Coons, James C.; Denny, Joshua C.; Dillon, Chrisly; Elsey, Amanda R.; Hamadeh, Issam S.; Harada, Shuko; Hillegass, William B.; Hines, Lindsay; Horenstein, Richard B.; Howell, Lucius A.; Jeng, Linda J.B.; Kelemen, Mark D.; Lee, Y. M.; Magvanjav, Oyunbileg; Montasser, May; Nelson, David R.; Nutescu, Edith A.; Nwaba, Devon C.; Pakyz, Ruth E.; Palmer, Kathleen; Peterson, Josh F.; Pollin, Toni I.; Quinn, Alison H.; Robinson, Shawn W.; Schub, Jamie; Skaar, Todd; Smith, D. Max; Sriramoju, Vindhya B.; Starostik, Petr; Stys, Tomasz P.; Stevenson, James M.; Varunok, Nicholas; Vesely, Mark R.; Wake, Dyson T.; Weck, Karen E.; Weitzel, Kristin W.; Wilke, Russell A.; Willig, James; Zhao, Richard Y.; Kreutz, Rolf; Stouffer, George A.; Empey, Philip E.; Limdi, Nita A.; Shuldiner, Alan R.; Winterstein, Almut G.; Johnson, Julie A.

In: JACC: Cardiovascular Interventions, 01.01.2017.

Research output: Contribution to journalArticle

Cavallari, LH, Lee, CR, Beitelshees, AL, Cooper-DeHoff, RM, Duarte, JD, Voora, D, Kimmel, SE, McDonough, CW, Gong, Y, Dave, CV, Pratt, VM, Alestock, TD, Anderson, RD, Alsip, J, Ardati, AK, Brott, BC, Brown, L, Chumnumwat, S, Clare-Salzler, MJ, Coons, JC, Denny, JC, Dillon, C, Elsey, AR, Hamadeh, IS, Harada, S, Hillegass, WB, Hines, L, Horenstein, RB, Howell, LA, Jeng, LJB, Kelemen, MD, Lee, YM, Magvanjav, O, Montasser, M, Nelson, DR, Nutescu, EA, Nwaba, DC, Pakyz, RE, Palmer, K, Peterson, JF, Pollin, TI, Quinn, AH, Robinson, SW, Schub, J, Skaar, T, Smith, DM, Sriramoju, VB, Starostik, P, Stys, TP, Stevenson, JM, Varunok, N, Vesely, MR, Wake, DT, Weck, KE, Weitzel, KW, Wilke, RA, Willig, J, Zhao, RY, Kreutz, R, Stouffer, GA, Empey, PE, Limdi, NA, Shuldiner, AR, Winterstein, AG & Johnson, JA 2017, 'Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention', JACC: Cardiovascular Interventions. https://doi.org/10.1016/j.jcin.2017.07.022
Cavallari, Larisa H. ; Lee, Craig R. ; Beitelshees, Amber L. ; Cooper-DeHoff, Rhonda M. ; Duarte, Julio D. ; Voora, Deepak ; Kimmel, Stephen E. ; McDonough, Caitrin W. ; Gong, Yan ; Dave, Chintan V. ; Pratt, Victoria M. ; Alestock, Tameka D. ; Anderson, R. David ; Alsip, Jorge ; Ardati, Amer K. ; Brott, Brigitta C. ; Brown, Lawrence ; Chumnumwat, Supatat ; Clare-Salzler, Michael J. ; Coons, James C. ; Denny, Joshua C. ; Dillon, Chrisly ; Elsey, Amanda R. ; Hamadeh, Issam S. ; Harada, Shuko ; Hillegass, William B. ; Hines, Lindsay ; Horenstein, Richard B. ; Howell, Lucius A. ; Jeng, Linda J.B. ; Kelemen, Mark D. ; Lee, Y. M. ; Magvanjav, Oyunbileg ; Montasser, May ; Nelson, David R. ; Nutescu, Edith A. ; Nwaba, Devon C. ; Pakyz, Ruth E. ; Palmer, Kathleen ; Peterson, Josh F. ; Pollin, Toni I. ; Quinn, Alison H. ; Robinson, Shawn W. ; Schub, Jamie ; Skaar, Todd ; Smith, D. Max ; Sriramoju, Vindhya B. ; Starostik, Petr ; Stys, Tomasz P. ; Stevenson, James M. ; Varunok, Nicholas ; Vesely, Mark R. ; Wake, Dyson T. ; Weck, Karen E. ; Weitzel, Kristin W. ; Wilke, Russell A. ; Willig, James ; Zhao, Richard Y. ; Kreutz, Rolf ; Stouffer, George A. ; Empey, Philip E. ; Limdi, Nita A. ; Shuldiner, Alan R. ; Winterstein, Almut G. ; Johnson, Julie A. / Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. In: JACC: Cardiovascular Interventions. 2017.
@article{340be26238014004a5fb9e0372046b2a,
title = "Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention",
abstract = "Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results: Among 1,815 patients, 572 (31.5{\%}) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95{\%} confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95{\%} confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95{\%} confidence interval: 0.69 to 1.88; p = 0.60). Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.",
keywords = "Antiplatelet therapy, Cardiovascular events, Clopidogrel, CYP2C19, Percutaneous coronary intervention, Pharmacogenomics",
author = "Cavallari, {Larisa H.} and Lee, {Craig R.} and Beitelshees, {Amber L.} and Cooper-DeHoff, {Rhonda M.} and Duarte, {Julio D.} and Deepak Voora and Kimmel, {Stephen E.} and McDonough, {Caitrin W.} and Yan Gong and Dave, {Chintan V.} and Pratt, {Victoria M.} and Alestock, {Tameka D.} and Anderson, {R. David} and Jorge Alsip and Ardati, {Amer K.} and Brott, {Brigitta C.} and Lawrence Brown and Supatat Chumnumwat and Clare-Salzler, {Michael J.} and Coons, {James C.} and Denny, {Joshua C.} and Chrisly Dillon and Elsey, {Amanda R.} and Hamadeh, {Issam S.} and Shuko Harada and Hillegass, {William B.} and Lindsay Hines and Horenstein, {Richard B.} and Howell, {Lucius A.} and Jeng, {Linda J.B.} and Kelemen, {Mark D.} and Lee, {Y. M.} and Oyunbileg Magvanjav and May Montasser and Nelson, {David R.} and Nutescu, {Edith A.} and Nwaba, {Devon C.} and Pakyz, {Ruth E.} and Kathleen Palmer and Peterson, {Josh F.} and Pollin, {Toni I.} and Quinn, {Alison H.} and Robinson, {Shawn W.} and Jamie Schub and Todd Skaar and Smith, {D. Max} and Sriramoju, {Vindhya B.} and Petr Starostik and Stys, {Tomasz P.} and Stevenson, {James M.} and Nicholas Varunok and Vesely, {Mark R.} and Wake, {Dyson T.} and Weck, {Karen E.} and Weitzel, {Kristin W.} and Wilke, {Russell A.} and James Willig and Zhao, {Richard Y.} and Rolf Kreutz and Stouffer, {George A.} and Empey, {Philip E.} and Limdi, {Nita A.} and Shuldiner, {Alan R.} and Winterstein, {Almut G.} and Johnson, {Julie A.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.jcin.2017.07.022",
language = "English (US)",
journal = "JACC: Cardiovascular Interventions",
issn = "1936-8798",
publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

AU - Cavallari, Larisa H.

AU - Lee, Craig R.

AU - Beitelshees, Amber L.

AU - Cooper-DeHoff, Rhonda M.

AU - Duarte, Julio D.

AU - Voora, Deepak

AU - Kimmel, Stephen E.

AU - McDonough, Caitrin W.

AU - Gong, Yan

AU - Dave, Chintan V.

AU - Pratt, Victoria M.

AU - Alestock, Tameka D.

AU - Anderson, R. David

AU - Alsip, Jorge

AU - Ardati, Amer K.

AU - Brott, Brigitta C.

AU - Brown, Lawrence

AU - Chumnumwat, Supatat

AU - Clare-Salzler, Michael J.

AU - Coons, James C.

AU - Denny, Joshua C.

AU - Dillon, Chrisly

AU - Elsey, Amanda R.

AU - Hamadeh, Issam S.

AU - Harada, Shuko

AU - Hillegass, William B.

AU - Hines, Lindsay

AU - Horenstein, Richard B.

AU - Howell, Lucius A.

AU - Jeng, Linda J.B.

AU - Kelemen, Mark D.

AU - Lee, Y. M.

AU - Magvanjav, Oyunbileg

AU - Montasser, May

AU - Nelson, David R.

AU - Nutescu, Edith A.

AU - Nwaba, Devon C.

AU - Pakyz, Ruth E.

AU - Palmer, Kathleen

AU - Peterson, Josh F.

AU - Pollin, Toni I.

AU - Quinn, Alison H.

AU - Robinson, Shawn W.

AU - Schub, Jamie

AU - Skaar, Todd

AU - Smith, D. Max

AU - Sriramoju, Vindhya B.

AU - Starostik, Petr

AU - Stys, Tomasz P.

AU - Stevenson, James M.

AU - Varunok, Nicholas

AU - Vesely, Mark R.

AU - Wake, Dyson T.

AU - Weck, Karen E.

AU - Weitzel, Kristin W.

AU - Wilke, Russell A.

AU - Willig, James

AU - Zhao, Richard Y.

AU - Kreutz, Rolf

AU - Stouffer, George A.

AU - Empey, Philip E.

AU - Limdi, Nita A.

AU - Shuldiner, Alan R.

AU - Winterstein, Almut G.

AU - Johnson, Julie A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

AB - Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

KW - Antiplatelet therapy

KW - Cardiovascular events

KW - Clopidogrel

KW - CYP2C19

KW - Percutaneous coronary intervention

KW - Pharmacogenomics

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DO - 10.1016/j.jcin.2017.07.022

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