Aspirin Resistance in Chinese Stroke Patients Increased the Rate of Recurrent Stroke and other Vascular Events

Yi, Xingyang; Zhou, Qiang; Lin, Jing; Chi, Lifen

doi:10.1111/j.1747-4949.2012.00929.x

Cited by 64 publications

(62 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet aggregation activity was measured using light transmittance aggregometry before clopidogrel treatment and within 7–10 days after clopidogrel treatment according to a previous study 21) . In brief, 5 mL of fasting venous blood was collected in 660 µL of 3.8% sodium citrate and centrifuged at 200 × g for 10 min to obtain platelet-rich plasma (PRP).…”

Section: Methodsmentioning

confidence: 99%

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

Lin

Wang

et al. 2016

J Atheroscler Thromb

Self Cite

View full text Add to dashboard Cite

Aims: Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation.Methods: A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7 – 10 day treatment. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS).Results: Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS > 2 points) compared with clopidogrel-sensitive patients.Conclusion: CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

Lin

Wang

et al. 2016

J Atheroscler Thromb

Self Cite

View full text Add to dashboard Cite

show abstract

“…Platelet aggregation was measured by light transmittance aggregometry (LTA), as described previously [2, 5, 18]. A mean aggregation of ≥70% with 10 μM ADP and a mean aggregation of ≥20% with 0.5 mM AA after aspirin intake for 7 to 10 days were defined as AR.…”

Section: Methodsmentioning

confidence: 99%

“…Aspirin is routinely used for the treatment of IS [3], and its use is associated with improved outcomes [2, 4]. However, recent studies have shown that aspirin resistance (AR) can lead to the failure of antiplatelet therapy [5], and is associated with frequent END and ERIS in patients with acute IS [6, 7]. Thus, further identification of risk factors for AR could improve the treatment of patients at risk of IS, enabling clinicians to choose more effective treatments.…”

Section: Introductionmentioning

confidence: 99%

Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients

Chün

Zhou

et al. 2017

BMC Neurol

Self Cite

View full text Add to dashboard Cite

BackgroundThe effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS).MethodsA total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7–10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2, GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10 days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10 days of admission.Results175 (20.6%) patients were AR, 45 (5.3%) were aspirin semi-resistant, 121 (14.2%) developed END, 17 (0.2%) had ERIS, 2 (0.2%) died, and 6 (0.7%) had MI. Single locus analysis indicated that only rs1371097 was associated with AR. However, GMDR analysis indicated that the following three sets of gene-gene interactions were significantly associated with AR: rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097CT/rs2317676AG. END occurred significantly more frequently in patients with AR or high-risk interactive genotypes. Moreover, AR and high-risk interactive genotypes were independently associated with END.ConclusionSensitivity of IS patients to aspirin and END may be multifactorial and is not significantly associated with a single gene polymorphism. Combinational analysis may useful for further insight into the genetic risks for AR.

show abstract

“…None of the studies published to date have been adequately powered to definitively comment on whether ex vivo HTPR status on platelet function testing in CVD patients predicts the risk of recurrent vascular events. Evidence pertaining to the relationship between antiplatelet-HTPR status and functional outcome, stroke severity and mortality on antiplatelet therapy following TIA or stroke is emerging, but available data from small-medium sized studies need to be validated in larger studies [51,64,66,92,93]. Furthermore, with the exception of three studies [45,51,64], duration of clinical follow-up has been relatively short.…”

Section: Discussionmentioning

confidence: 99%

“…A recent cross-sectional study in CVD patients with prospective follow-up assessed ex vivo 'aspirin resistance' in 634 Chinese stroke patients on 200 mg of aspirin daily with optical aggregometry using PRP [51]. Aspirin resistance (AR) was defined as a mean aggregation of !…”

Section: Platelet Aggregometrymentioning

confidence: 99%

Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature

et al. 2015

View full text Add to dashboard Cite

The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100 Õ , VerifyNow Õ and Multiplate Õ ). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p50.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p ¼ 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are urgently needed to determine whether comprehensive assessment of HTPR at high and low shear stress with a range of user-friendly whole blood platelet function testing platforms, in conjunction with pharmacogenetic data, improves our ability to predict the risk of recurrent vascular events in CVD patients, and thus enhance secondary prevention following TIA or ischaemic stroke.

show abstract

Aspirin Resistance in Chinese Stroke Patients Increased the Rate of Recurrent Stroke and other Vascular Events

Cited by 64 publications

References 21 publications

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients

Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature

Contact Info

Product

Resources

About