Factors that contribute to clopidogrel resistance in cardiovascular disease patients: environmental and genetic approach

Al‐Azzam, Sayer; Alzoubi, Karem H.; Khabour, Omar F.; Nusair, Mohammad B.; Al-Hadidi, Hakam; Awidi, Abdalla; Saleh, Akram

doi:10.5414/cp201784

Cited by 25 publications

(32 citation statements)

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“…Another limitation is the higher number of active smokers in the stroke group as compared to healthy subjects. Conflicting results exist about the effect of smoking on platelet function testing [20, 24, 34]. However in our study, ANCOVA analysis was used to control for the effect of smoking.…”

Section: Discussionmentioning

confidence: 98%

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

et al. 2016

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BackgroundThere is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin.MethodsPatients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL).ResultsSeventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min.ConclusionsMany patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing.

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Section: Discussionmentioning

confidence: 98%

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

et al. 2016

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“…It has been already described by many authors [8][9][10][11][12]31] that the resistance to clopidogrel therapy is encoded by the Ã second and the Ã third alleles of CYP2C19. These hepatic enzymes open the thio-ring of clopidogrel.…”

Section: Discussionmentioning

confidence: 99%

“…The variant alleles Ã 2 and Ã 3 of CYP2C19 represent loss-of-function alleles, which encode hypofunctional enzyme and are responsible for lower rates of biotransformation of clopidogrel into an active metabolite [7][8][9][10][11][12]. Clopidogrel is a pro-drug and must be activated by two steps of hepatic P450 system enzymes, such as CYP2C19, CYP2B6, CYP3A4, CYP1A2, CYP2C9, CYP2D6, CYP3A5.…”

Section: Introductionmentioning

confidence: 99%

The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy

Tatarūnas¹,

Jankauskienė²,

Kupstytė

et al. 2014

Blood Coagulation &Amp; Fibrinolysis

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Dual antiplatelet therapy with aspirin and clopidogrel is used to lower the risk of arterial thrombosis. However, this strategy is not always successful owing to high interindividual variability in response to antiplatelet therapy. To evaluate an impact of CYP2C19 G681A and CYP4F2 G1347A polymorphisms and clinical factors on dual antiplatelet effect of clopidogrel and aspirin. Totally 89 patients who continued dual aspirin and clopidogrel antiplatelet therapy for at least of 14 days were included into the further study. Test for platelet aggregation was performed according to the classical Born method. Genotyping of CYP2C19*2 and CYP2C19*3 and CYP4F2*3 was done by using commercial probes from Applied Biosystems (UK). Patient age, weight and body weight index did not correlate significantly with platelet aggregation level both induced by ADP and epinephrine (P > 0.05). Serum concentration of creatinine, diabetes, angiotensin II receptor blockers, B-blockers, statin or omeprazole use had no significant effect on platelet aggregation. The users of angiotensin-converting enzyme inhibitors had lower platelet aggregation levels with epinephrine vs. nonusers: 28.80 ± 13.25 vs. 51.15 ± 23.50, P < 0.03, respectively. Platelet aggregation with ADP was higher in CYP2C19*1*2 genotype carriers than in CYP2C19*1*1 carriers (P = 0.01). Platelet aggregation with epinephrine was higher in CYP4F2 GA genotype carriers than in GG (P = 0.04) or AA (P = 0.01) carriers. Our study confirms that CYP2C19 G681A genotype has an impact on antiplatelet effect of clopidogrel. The novelty is that the platelet aggregation after induction with epinephrine is influenced by CYP4F2 G1347A genotype.

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“…Several studies have assessed the role of Multiplate analysis in patients treated with various antiplatelet medications and in a variety of cardiovascular, surgical and haematological conditions . However there have been few studies using the Multiplate device in assessing the response to Aspirin therapy and the device has not been used previously in patients presenting with acute cerebrovascular events.…”

Section: Discussionmentioning

confidence: 99%

The clinical utility of Multiplate analyser measurement in platelet function testing following stroke and transient ischaemic attack

Mannu

Macartney

Lambert³

et al. 2014

European J of Haematology

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Factors that contribute to clopidogrel resistance in cardiovascular disease patients: environmental and genetic approach

Abstract: Several factors might contribute to clopidogrel resistance including gender, concomitant use of calcium channel blockers, HDL and CYP2C19*2 polymorphism.

Cited by 25 publications

References 0 publications

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy

The clinical utility of Multiplate analyser measurement in platelet function testing following stroke and transient ischaemic attack

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