ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome

2007 ◽  
Vol 98 (10) ◽  
pp. 838-843 ◽  
Author(s):  
Corinne Frere ◽  
Thomas Cuisset ◽  
Jacques Quilici ◽  
Laurence Camoin ◽  
Joseph Carvajal ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Roc Curves ◽  
Coronary Intervention ◽  
Reactivity Index ◽  
Predictive Values ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
St Elevation ◽  
Ischemic Events

SummaryClopidogrel responsiveness has been proposed to be involved in recurrent ischemic events after stenting for non-ST elevation acute coronary syndromes (NSTE ACS). However, its biological definition is not consensual. We assess the value ofADP-induced platelet aggregation (ADP-Ag) and platelet reactivity indexVASP (PRI VASP) in predicting recurrent ischemic events in patients with NSTE ACS undergoing percutaneous coronary intervention (PCI). We studied 195 consecutive NSTE ACS patients undergoing PCI after a 600 mg loading dose of clopidogrel. ADPAg and PRI VASP were analysed. The primary end-point was recurrent ischemic events within 30 days of PCI. It occurred in 14 patients (7%). Construction of ROC curves to examine the value of predictive models showed that sensitivity and specificity for primary endpoint were 79% and 76%, respectively, for a maximal intensity of ADP-Ag ≥70%, 93% and 50% for PRIVASP> 53%. The positive and negative predictive values were 21% and 98%, respectively, for ADP-Ag ≥70%, 12% and 99% for PRIVASP> 53%. In patients with NSTE ACS undergoing PCI, ADP-Ag and PRI VASP identify low responders to clopidogrel with an increased risk of recurrent ischemic events with respective cut-off values of 70% and 53%.

Abstract 39: Platelet Reactivity to Prostaglandin E2 is a Novel Modifiable Risk Factor for St-Elevation Myocardial Infarction

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Eitan A Friedman ◽  
Elias V Haddad ◽  
Valentinas Joksas ◽  
Shi Huang ◽  
Meng Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Coronary Intervention ◽  
Prostaglandin E ◽  
Platelet Response ◽  
Increased Risk ◽  
St Elevation

Background: Patients with lower thresholds for platelet activation are at increased risk for primary and recurrent myocardial infarction (MI) and overall cardiovascular (CV) mortality. We have demonstrated that there are two phenotypes of platelet response to Prostaglandin E 2 (PGE 2 ), such that it increases threshold for aggregation in 45% of individuals (inhibitory) and lowers threshold for aggregation in 55% (potentiating). As PGE 2 is present in atherosclerotic plaques, and its receptors are present on platelets, biologic variability in PGE 2 responses may have clinical implications. We hypothesized that patients with higher thresholds for platelet activation would have a lower risk of thrombotic CV events, specifically ST-Elevation MI (STEMI). Methods: 85 patients undergoing percutaneous coronary intervention for stable or unstable coronary disease were phenotyped for PGE 2 response. Platelet rich plasma was treated with various concentrations of U46,619 (thromboxane agonist) with or without PGE 2 100 nM, and phenotype determined by light aggregometry. Analysis of the maximum PGE 2 effect (maximum aggregation with PGE 2 minus maximum aggregation without it) was performed using linear and non-linear statistical methods. Results: Traditional cardiovascular risk factors were similar between groups. A higher percentage of patients with the potentiating phenotype had a history of STEMI than those with the inhibitory phenotype. Logistic regression using restricted cubic spline showed that the predicted probabilities of STEMI increased from 0.04 (at the strongest inhibitory phenotype) to 0.43 (at the median phenotype). The OR of phenotype at the median relative to that at the 10th quantile was 7.4 (95 % CI=1.6, 34.8). Conclusions: PGE 2 inhibitory phenotype confers a decreased lifetime risk of STEMI in individuals at high risk for CV events. We have previously shown that an EP3 receptor antagonist converts the potentiating to the inhibitory phenotype. Thus, the PGE2 phenotype may be a novel marker of cardiovascular risk that may also identify patients who would benefit from an EP3 antagonist.

Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

2013 ◽  
Vol 110 (12) ◽  
pp. 1223-1231 ◽  
Author(s):  
Dominick J. Angiolillo ◽  
Jose L. Ferreiro ◽  
Joseph A. Jakubowski ◽  
Kenneth J. Winters ◽  
Mark B. Effron ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Active Metabolite ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Coronary Syndrome ◽  
Metabolite Generation ◽  
Artery Disease ◽  
The Impact

SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

Association between inflammatory biomarkers and platelet aggregation in patients under chronic clopidogrel treatment

2010 ◽  
Vol 104 (12) ◽  
pp. 1193-1200 ◽  
Author(s):  
Isabell Bernlochner ◽  
Steven Steinhubl ◽  
Siegmund Braun ◽  
Tanja Morath ◽  
Juliane Jaitner ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Primary Outcome Measure ◽  
Reactive Protein ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Inflammatory Processes ◽  
Independent Association ◽  
Wbc Count

SummaryInflammatory processes in the vessel wall are associated with progression of atherosclerosis and myocardial infarction. Both high levels of C-reactive protein (CRP) and high on-clopidogrel treatment platelet reactivity (HPR) have been linked to an increased risk of ischaemic events after percutaneous coronary intervention (PCI). The aim of this study was to explore the association between biomarker levels of inflammation and platelet reactivity. Stable patients (n=1,223) eligible for this study were under chronic antiplatelet treatment with aspirin and clopidogrel due to prior coronary stent placement. ADP-induced platelet aggregation (in AU*min) was measured on a Multiplate analyser. The primary outcome measure of this retrospective study was the ADP-induced platelet aggregation in patients with versus those without elevated CRP levels. Of the patients 15.5% (n=189) showed elevated CRP levels (≥5 mg/l). Platelet aggregation (median [interquartile range]) was significantly higher in patients with elevated CRP levels compared to patients with normal (<5 mg/l) CRP levels (305 [202–504] AU*min vs. 218 [144–384] AU*min; p<0.001). A multivariable linear regression model that adjusted for known predictors of HPR confirmed a significant independent association between elevated CRP levels and high ADP-induced platelet aggregation values (p=0.0002). Elevated WBC count and fibrinogen levels were also associated with higher platelet aggregation values (p<0.001 for both). In conclusion, elevated levels of CRP, WBC count and fibrinogen were significantly associated with high platelet reactivity in patients under chronic clopidogrel treatment. Whether a direct relation between platelets and inflammation exists, as well as the clinical impact of our results, warrants further investigations.

Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome

2015 ◽  
Vol 114 (10) ◽  
pp. 702-707 ◽  
Author(s):  
Marc Laine ◽  
Laurence Camoin-Jau ◽  
Frederic Noirot ◽  
Régis Guieu ◽  
Françoise Dignat-George ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Receptor Blockade ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
Adp Receptor ◽  
The Mean

SummaryPretreatment with a loading dose (LD) of clopidogrel or ticagrelor before percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is supported by the guidelines, but debated following a recent meta-analysis on clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel pretreatment failed to reduce ischaemic events. The timing of optimal platelet reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS (NSTE ACS) is yet undetermined. In the present study, we aimed to investigate the delay required to reach optimal PR inhibition in NSTE ACS following a LD of ticagrelor or prasugrel. Consecutive patients undergoing PCI for NSTE ACS were randomised in this monocentre study. The Vasodilatorphosphoprotein index (VASP) was used to measure PR before the LD and then at 30 minutes, 1, 2, 4 and 24 hours (h) post-LD. Optimal PR inhibition was defined as a VASP< 50 %. We randomised 24 patients to ticagrelor or prasugrel LD. One hour after the LD, 29 % of patients had a VASP > 50 % (ticagrelor and prasugrel: 25 vs 33 %; p=0.7). Optimal PR inhibition was obtained 2 h after the LD in both groups (12/12 with ticagrelor and 11/12 with prasugrel). At that time, the mean VASP index was 19 ± 16 % (95 %CI: 12–25). Maximal PR inhibition was reached after 4 h: 11 ± 10 % (95 %CI: 6–15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal inhibition within 4 h.

High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes

2007 ◽  
Vol 97 (02) ◽  
pp. 282-287 ◽  
Author(s):  
Corinne Frere ◽  
Jacques Quilici ◽  
Pierre-Emmanuel Morange ◽  
Lyassine Nait-Saidi ◽  
Christopher Mielot ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Acute Coronary Syndromes ◽  
Troponin I ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Post Treatment ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
St Elevation

SummaryHigh post-treatment platelet reactivity (HPPR= adenosine diphosphate [ADP] 10 µM-induced platelet aggregation > 70%) identifies low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for non-ST elevation acute coronary syndromes (NSTEACS). This study was designed to compare the incidence of periprocedural myocardial infarction (MI) after stenting for NSTEACS patients between non-responders to dual antiplatelet therapy defined by HPPR and normo-responders. One hundred ninety NSTE-ACS consecutive patients undergoing coronary stenting were included in this prospective study. They received 250 mg aspirin and a 600 mg loading dose of clopidogrel at least 12 hours (h) before percutaneous coronary intervention (PCI). A single post-treatment blood sample was obtained before PCI to analyze maximal intensity of ADP-induced platelet aggregation, and troponin levels were analyzed before PCI, and 12 and 24 h after PCI. Troponin I was considered elevated if > 0.4 ng/ ml. HPPR was present in 22% of patients (n=42). Periprocedural MI occurred significantly more frequently in patients with HPPR than in the normo-responders (43% vs. 24%, p=0.014). After being correlated with recurrent ischemic events after stenting for NSTE-ACS, the HPPR seems to be also a marker of increased risk of periprocedural MI for NSTE-ACS patients.

scholarly journals Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

2017 ◽  
Vol 24 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Peng Ding ◽  
Yujie Wei ◽  
Nana Chen ◽  
Huiliang Liu
Keyword(s):  
Acute Coronary Syndrome ◽  
Healthy Volunteers ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

Biological efficacy of a 600 mg loading dose of clopidogrel in ST-elevation myocardial infarction

2012 ◽  
Vol 108 (07) ◽  
pp. 101-106 ◽  
Author(s):  
Julie Berbis ◽  
Marc Laine ◽  
Sébastien Armero ◽  
Jacques Bessereau ◽  
Laurent Jacquin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Fibrinogen Level ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Individual Variability ◽  
St Elevation Myocardial Infarction ◽  
Loading Dose ◽  
Coronary Syndrome ◽  
St Elevation

SummaryOptimal platelet reactivity (PR) inhibition is critical to prevent thrombotic events in primary percutaneous coronary intervention (PCI). We aimed to determine the relationship between high on-treatment platelet reactivity (HTPR) and ST-elevation myocardial infarction (STEMI) following a 600 mg loading dose (LD) of clopidogrel. We performed a prospective monocentre study enrolling patients on clopidogrel undergoing PCI. The VASP index was used to assess PR inhibition after clopidogrel LD. HTPR was defined according to the consensus as a VASP index ≥50%. The present study included 833 patients undergoing PCI. Most patients had PCI for an acute coronary syndrome (58.7%). The mean VASP index was 50 ± 23% with a large inter-individual variability (range: 1–94%). Patients with a VASP index ≥50% were significantly older (p= 0.03), with a higher body mass index (BMI) (p<0.001), more often diabetic (p=0.03), taking omeprazole (p=0.03), admitted for an acute coronary syndrome (ACS) and with a high fibrinogen level compared to good responders (VASP <50%). In multivariate analysis BMI, omeprazole use, ACS and high fibrinogen level (p<0.001) remained significantly associated with HTPR. Of importance, in this analysis STEMI was independently associated with HTPR when compared with the other forms of ACS (NSTEMI and unstable angina) with an odd ratio of 2.14 (95% CI: 1.3 –3.5; p=0.003). In conclusion, STEMI is associated with high on-treatment platelet reactivity following 600 mg of clopidogrel. The present results suggest that 600 mg of clopidogrel may not be able to achieve an optimal PR inhibition in STEMI patients undergoing PCI and more potent drugs may be preferred.

Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: Insights from the switching anti-platelet (SWAP) study

2013 ◽  
Vol 109 (02) ◽  
pp. 347-355 ◽  
Author(s):  
Dominick Angiolillo ◽  
Roger DeRaad ◽  
Andrew Frelinger ◽  
Paul Gurbel ◽  
Timothy Costigan ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cytochrome P450 ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Maintenance Phase ◽  
Reactivity Index ◽  
Loading Dose ◽  
Cyp2c19 Genotype ◽  
Coronary Syndrome ◽  
Clopidogrel Therapy

SummaryThe prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥50%). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p>0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥50% (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.

CYP2C19*2 and *3 Polymorphisms Are Associated with High Post- Treatment Platelet Reactivity in Korean Patients with Acute Coronary Syndrome Undergoing Percutanous Coronary Intervention.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 982-982
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Gyeong-Won Lee
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Post Treatment ◽  
Light Transmittance ◽  
Platelet Response ◽  
Korean Patients ◽  
Coronary Syndrome ◽  
Percutanous Coronary Intervention

Abstract Background: Cytochrome P450 (CYP) 2C19 is an enzyme showing genetic polymorphism that may cause marked interindividual and interethnic variation in the metabolism and disposition of its substrates. CYP2C19*2 and CYP2C19*3 are the most common of CYP2C19 polymorphisms, and show phenotypic poor metabolism. Recent data have shown that the CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet response to clopidogrel in healthy controls and Caucasian patients with acute coronary syndrome. However, It is unknown whether CYP2C19 *3, which is frequently noted in Asian, is also associated with platelet response to clopidogrel. Therefore, this study was conducted to analyze the effect of CYP2C19 *2 and *3 polymorphisms on high post-treatment platelet reactivity (HPPR) on clopidogrel in Korean patients with acute coronary syndrome, as a representative of Asian populations. Methods: The study included 136 consecutive patients undergoing percutanous coronary intervention (PCI). Adenosine diphosphate (ADP)-induced platelet aggregation by light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay (Ultegra rapid platelet function assay; Accumetrics Inc., USA) were assessed after a loading dose and after the maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by Snapshot method. Results: The genotypic distributions of CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3 were 57 (41.9%), 47 (34.6%), 12 (8.8%), 14 (10.3%), 6 (4.4%), and 6(4.4%), respectively. The frequencies of CYP2C19 mutant alleles in Korean were higher than Caucasians. The CYP2C19*2 and CYP2C19*3 polymorphisms were significantly associated with persistent higher platelet aggregation by LTA, and lower inhibition of platelet reactivity by VerifyNow P2Y12 assay after clopidogrel than CYP2C19*1 genotype. The CYP2C19*2 and *3 alleles were more frequent in clopidogrel hyporesponsiveness, defined by persistent HPPR (5 uM ADP-induced platelet aggregation >50%; p = 0.01). Conclusions: This study suggests that the CYPC19*2 and *3 alleles influence clopidogrel hyporesponsiveness after clopidogrel in Asian patients with acute coronary syndromes undergoing PCI. These findings can have a significant impact on the future design of pharmacognetic antiaggregant strategies for acute coronary syndrome on antiplatelet treatment.

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