Aspirin and clopidogrel high on‐treatment platelet reactivity and genetic predictors in peripheral arterial disease
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...
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| Published in: | Catheterization and cardiovascular interventions Vol. 91; no. 7; pp. 1308 - 1317 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.06.2018
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| ISSN: | 1522-1946, 1522-726X, 1522-726X |
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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. |
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| AbstractList | ObjectivesOur 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).BackgroundThe association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear.MethodsThis 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.ResultsThe 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).ConclusionClopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD. 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. 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).OBJECTIVESOur 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).The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear.BACKGROUNDThe association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear.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.METHODSThis 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.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).RESULTSThe 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).Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.CONCLUSIONClopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD. 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). The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. 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. 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). Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD. |
| Author | Westin, Gregory G. Anderson, David Armstrong, Ehrin J. Yeo, Khung‐Keong Li, Chin‐Shang Hua, Amy Chiamvimonvat, Nipavan Laird, John R. Amsterdam, Ezra A. López, Javier E. Chen, Debbie C. Singapuri, Anil |
| AuthorAffiliation | 3 Division of Cardiology, VA Eastern Colorado Healthcare System, CO 1 Division of Cardiovascular Medicine and the Vascular Center, University of California, Davis, CA 9 Department of Veterans Affairs, Northern California Health Care System, Mather, CA 5 Department of Medicine, Massachusetts General Hospital, Boston, MA 7 Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA 8 Department of Internal Medicine, University of California, San Francisco, CA 6 Division of Vascular and Endovascular Surgery, NYU Langone Medical Center, New York, NY 4 Division of Cardiovascular Medicine, University of California, Davis, CA 2 Department of Cardiology, National Heart Centre Singapore, Singapore |
| AuthorAffiliation_xml | – name: 6 Division of Vascular and Endovascular Surgery, NYU Langone Medical Center, New York, NY – name: 7 Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA – name: 2 Department of Cardiology, National Heart Centre Singapore, Singapore – name: 8 Department of Internal Medicine, University of California, San Francisco, CA – name: 1 Division of Cardiovascular Medicine and the Vascular Center, University of California, Davis, CA – name: 4 Division of Cardiovascular Medicine, University of California, Davis, CA – name: 5 Department of Medicine, Massachusetts General Hospital, Boston, MA – name: 9 Department of Veterans Affairs, Northern California Health Care System, Mather, CA – name: 3 Division of Cardiology, VA Eastern Colorado Healthcare System, CO |
| Author_xml | – sequence: 1 givenname: Khung‐Keong orcidid: 0000-0002-5457-4881 surname: Yeo fullname: Yeo, Khung‐Keong organization: National Heart Centre Singapore – sequence: 2 givenname: Ehrin J. orcidid: 0000-0002-5682-8363 surname: Armstrong fullname: Armstrong, Ehrin J. organization: VA Eastern Colorado Healthcare System – sequence: 3 givenname: Javier E. surname: López fullname: López, Javier E. organization: University of California – sequence: 4 givenname: Debbie C. surname: Chen fullname: Chen, Debbie C. organization: Massachusetts General Hospital – sequence: 5 givenname: Gregory G. surname: Westin fullname: Westin, Gregory G. organization: NYU Langone Medical Center – sequence: 6 givenname: Chin‐Shang surname: Li fullname: Li, Chin‐Shang organization: University of California – sequence: 7 givenname: David surname: Anderson fullname: Anderson, David organization: University of California – sequence: 8 givenname: Amy surname: Hua fullname: Hua, Amy organization: University of California – sequence: 9 givenname: Anil surname: Singapuri fullname: Singapuri, Anil organization: University of California – sequence: 10 givenname: Ezra A. surname: Amsterdam fullname: Amsterdam, Ezra A. organization: University of California – sequence: 11 givenname: Nipavan surname: Chiamvimonvat fullname: Chiamvimonvat, Nipavan organization: Northern California Health Care System – sequence: 12 givenname: John R. surname: Laird fullname: Laird, John R. email: Lairdjr@ah.org organization: University of California |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29411531$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_2459_JCM_0000000000001406 crossref_primary_10_1016_j_ejvs_2018_06_032 crossref_primary_10_26453_otjhs_905082 crossref_primary_10_1016_j_ejvs_2021_10_045 crossref_primary_10_1016_j_thromres_2024_02_010 crossref_primary_10_2147_IJGM_S450059 crossref_primary_10_1080_09537104_2020_1742314 crossref_primary_10_1016_j_avsg_2022_12_071 crossref_primary_10_1177_17085381231214324 crossref_primary_10_2147_PGPM_S279719 crossref_primary_10_1186_s12959_022_00445_4 crossref_primary_10_1093_ajhp_zxac095 crossref_primary_10_1016_j_vph_2021_106925 |
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| Issue | 7 |
| Keywords | peripheral arterial disease genetics antiplatelet therapy |
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| Notes | Funding information American Heart Association Clinical Research Award, NIH, Grant/Award Number: R01 HL085727, R01 HL137228, and R01 HL085844; VA Merit Review, Grant/Award Number: I01 BX000576 and I01CX001490; Robert Wood Johnson Foundation, CTSC KL2; National Center for Advancing Translational Sciences, Grant/Award Number: UL1 TR000002, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Grant/Award Number: UL1 TR000002, UL1 TR001860. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 |
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Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on‐treatment platelet reactivity (HoTPR), and... Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse... ObjectivesOur aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on‐treatment platelet reactivity (HoTPR), and... |
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| SubjectTerms | Adult Aged Aged, 80 and over Amputation, Surgical Angiography antiplatelet therapy Arteries Aryldialkylphosphatase - genetics Arylesterase Aspirin Aspirin - adverse effects Aspirin - therapeutic use California - epidemiology Cardiovascular diseases Cerebral infarction Clinical outcomes Clopidogrel Clopidogrel - adverse effects Clopidogrel - therapeutic use Drug Resistance - genetics Drug Therapy, Combination Female genetics Group III Phospholipases A2 - genetics Health risk assessment Humans Limb Salvage Male Middle Aged Myocardial infarction Myocardial Infarction - epidemiology Paraoxonase Patients peripheral arterial disease Peripheral Arterial Disease - diagnosis Peripheral Arterial Disease - drug therapy Peripheral Arterial Disease - epidemiology Peripheral Arterial Disease - genetics Phospholipase A2 Platelet Aggregation Inhibitors - adverse effects Platelet Aggregation Inhibitors - therapeutic use Platelet Function Tests Platelets Polymorphism, Single Nucleotide Prospective Studies Risk Factors Single-nucleotide polymorphism Stroke - epidemiology Time Factors Treatment Outcome |
| Title | Aspirin and clopidogrel high on‐treatment platelet reactivity and genetic predictors in peripheral arterial disease |
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