Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease

Khung Keong Yeo, Ehrin J. Armstrong, Javier E Lopez, Debbie C. Chen, Gregory G. Westin, Chin-Shang Li, David Anderson, Amy Hua, Anil Singapuri, Ezra A Amsterdam, Nipavan Chiamvimonvat, John R. Laird

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). Background: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. Methods: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. Results: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU≥235 (52% freedom-from-event rate vs. 70% for PRU<235; P=0.09). TVR was higher in those with PRU≥235 (20 vs. 6%, unadjusted P=0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P=0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P=0.002). Conclusion: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

Original languageEnglish (US)
JournalCatheterization and Cardiovascular Interventions
DOIs
StateAccepted/In press - Jan 1 2018

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clopidogrel
Peripheral Arterial Disease
Aspirin
Blood Platelets
Therapeutics
Group III Phospholipases A2
Single Nucleotide Polymorphism
Extremities
Aryldialkylphosphatase

Keywords

  • Antiplatelet therapy
  • Genetics
  • Peripheral arterial disease

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease. / Yeo, Khung Keong; Armstrong, Ehrin J.; Lopez, Javier E; Chen, Debbie C.; Westin, Gregory G.; Li, Chin-Shang; Anderson, David; Hua, Amy; Singapuri, Anil; Amsterdam, Ezra A; Chiamvimonvat, Nipavan; Laird, John R.

In: Catheterization and Cardiovascular Interventions, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Objectives: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). Background: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. Methods: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. Results: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20{\%}) and clopidogrel HoTPR in 76 (49{\%}) patients. There was a trend toward more primary composite outcome events with PRU≥235 (52{\%} freedom-from-event rate vs. 70{\%} for PRU<235; P=0.09). TVR was higher in those with PRU≥235 (20 vs. 6{\%}, unadjusted P=0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P=0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P=0.002). Conclusion: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.",
keywords = "Antiplatelet therapy, Genetics, Peripheral arterial disease",
author = "Yeo, {Khung Keong} and Armstrong, {Ehrin J.} and Lopez, {Javier E} and Chen, {Debbie C.} and Westin, {Gregory G.} and Chin-Shang Li and David Anderson and Amy Hua and Anil Singapuri and Amsterdam, {Ezra A} and Nipavan Chiamvimonvat and Laird, {John R.}",
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T1 - Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease

AU - Yeo, Khung Keong

AU - Armstrong, Ehrin J.

AU - Lopez, Javier E

AU - Chen, Debbie C.

AU - Westin, Gregory G.

AU - Li, Chin-Shang

AU - Anderson, David

AU - Hua, Amy

AU - Singapuri, Anil

AU - Amsterdam, Ezra A

AU - Chiamvimonvat, Nipavan

AU - Laird, John R.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). Background: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. Methods: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. Results: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU≥235 (52% freedom-from-event rate vs. 70% for PRU<235; P=0.09). TVR was higher in those with PRU≥235 (20 vs. 6%, unadjusted P=0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P=0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P=0.002). Conclusion: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

AB - Objectives: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). Background: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. Methods: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. Results: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU≥235 (52% freedom-from-event rate vs. 70% for PRU<235; P=0.09). TVR was higher in those with PRU≥235 (20 vs. 6%, unadjusted P=0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P=0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P=0.002). Conclusion: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

KW - Antiplatelet therapy

KW - Genetics

KW - Peripheral arterial disease

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