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
Main Authors: Yeo, Khung‐Keong, Armstrong, Ehrin J., López, 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.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01.06.2018
Subjects:
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
California
peripheral arterial disease
genetics
antiplatelet therapy
ISSN:1522-1946, 1522-726X, 1522-726X
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Summary: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.
Bibliography: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.
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ISSN:1522-1946
1522-726X
1522-726X
DOI:10.1002/ccd.27453