Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study

2017 ◽  
Vol 117 (04) ◽  
pp. 727-733 ◽  
Author(s):  
Moshe Katz ◽  
Ehud Regev ◽  
Avi Sabbag ◽  
Israel Mazin ◽  
Arsalan Abu-Much ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Metabolic Activation ◽  
Platelet Inhibition ◽  
Standard Group ◽  
Loading Dose ◽  
Study Objective ◽  
Coronary Syndrome ◽  
Inhibition Of Platelet Aggregation ◽  
To Receive

SummaryIt was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (p< 0.001), and 84 % vs 77 % (p=0.59) at 4 h. Major adverse cardiac and cardiovascular events at 30 days were low (2 %), occurring in only one patient in the standard group. In conclusion, chewing a 180 mg ticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.Supplementary Material to this article is available online at www.thrombosis-online.com.

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.

scholarly journals Impact of selected genetic factors on clopidogrel inactive metabolite level and antiplatelet response in patients after percutaneous coronary intervention

2020 ◽  
Author(s):  
Urszula Adamiak-Giera ◽  
Anna Czerkawska ◽  
Szymon Olędzki ◽  
Mateusz Kurzawski ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Bleeding Risk ◽  
Metabolite Level ◽  
Coronary Syndrome ◽  
Inhibition Of Platelet Aggregation ◽  
Percutaneous Coronary ◽  
Inactive Metabolite ◽  
Before And After ◽  
Clopidogrel Therapy

Abstract Background and objective Clopidogrel is frequently used as part of optimal dual antiplatelet therapy in high-bleeding risk patients with the acute coronary syndrome. The concentration of the inactive carboxylic acid metabolite of clopidogrel might be useful to evaluate the response to clopidogrel therapy. Therefore, we sought to correlate the inhibition of platelet aggregation with the plasma level of the inactive metabolite of clopidogrel in patients after percutaneous coronary interventions (PCI) and their associations with the most frequently studied genetic polymorphisms. For this purpose, the fast and simple HPLC method for determining the concentration of the inactive metabolite was developed. Methods The effect of CYP2C19, CYP3A4/5, ABCB1 and PON1 genes on the plasma inactive metabolite concentration of clopidogrel and the platelet aggregation was investigated in 155 patients before and after PCI. Results The concentration of the inactive metabolite of clopidogrel was not significantly different in the intermediate metabolizers (IM) of CYP2C19 compared with extensive metabolizers (EM) both before and after PCI, while inhibition of platelet aggregation was found to be significantly better in EM than in IM. The presence of the A allele at position 2677 in the ABCB1 gene was associated with a significantly lower concentration of inactive metabolite of clopidogrel before PCI. Conclusion The CYP2C19*2 allele was associated with decreased platelet reactivity during clopidogrel therapy before and after PCI. Simultaneous determination of platelet aggregation and concentration of the inactive clopidogrel metabolite may be useful in clinical practice to find the cause of adverse effects or insufficient treatment effect in patients chronically treated with clopidogrel.

scholarly journals Relation of Functional Activity of Platelets to Prognosis of Unfavorable Cardiovascular Events in Patients with Acute Coronary Syndrome. Results of a Registry Study

Kardiologiia ◽  
2019 ◽  
Vol 59 (10) ◽  
pp. 5-13
Author(s):  
N. V. Lomakin ◽  
L. I. Buryachkovskaya ◽  
A. B. Sumarokov ◽  
Z. A. Gabbasov ◽  
A. N. Gerasimov
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Kidney Disease ◽  
Functional Activity ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Coronary Syndrome ◽  
C Statistic

Aim: to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS).Materials. The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets.Results. High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies.Conclusion. The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.

Abstract 3473: The Effect of Cigarette Smoking on the Antiplatelet Effect of Clopidogrel: The Smokers Paradox

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Gurbel ◽  
Joseph Dichiara ◽  
Kevin P Bliden ◽  
Mark J Antonino ◽  
Lawal Lookman
Keyword(s):  
Platelet Aggregation ◽  
Cigarette Smoking ◽  
Metabolic Activation ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Response Variability ◽  
Light Transmittance ◽  
Prior History ◽  
Platelet Response ◽  
Clopidogrel Therapy

Background: Wide response variability to clopidogrel therapy has been reported. Clopidogrel is a prodrug that requires metabolic activation by hepatic cytochromes (CYP). Cigarette smoking is an inducer of CYP1A2 and may, therefore, enhance the metabolism of clopidogrel. We sought to examine the effect of cigarette smoking on the platelet response to clopidogrel. Methods: Three hundred thirteen consecutive patients undergoing elective coronary stenting were studied. Platelet aggregation (PA) was assessed by light transmittance aggregometry (LTA) stimulated by 5 and 20μ M adenosine diphosphate. One hundred fourteen patients were on chronic clopidogrel therapy, were not reloaded, and had pre-stenting PA measurements. Pre-and post-stenting PA was measured in 199 patients: 60 were loaded with 300mg and 139 were loaded with 600mg. There were 120 current smokers (smoking within 2 weeks of PCI) and 193 non-smokers (no prior history of smoking). Low PA was defined as the lowest two quartiles of 5μM ADP-induced platelet aggregation (≤ 40%). Results: PA was significantly lower (p ≤ 0.008) in smokers on long term chronic clopidogrel treatment (Table ). Relative platelet inhibition (RPI) was higher in smokers treated with either 300mg or 600mg clopidogrel measured by 5 and 20μM ADP-induced PA. In a multivariate analysis, cigarette smoking was an independent predictor of low PA in patients on chronic clopidogrel therapy and in patients loaded with clopidogrel (r=0.3, p=0.0001). Conclusion: Clopidogrel therapy in smokers is associated with increased platelet inhibition and lower aggregation as compared to non-smokers. The mechanism of the smoking effect deserves further study and may be another cause of response variability to clopidogrel. RPI = 100 x ((baseline aggregation-post-treatment aggregation)/(baseline aggregation))

What Are Optimal P2Y12 Inhibitor and Schedule of Administration in Patients With Acute Coronary Syndrome?

2019 ◽  
Vol 25 (2) ◽  
pp. 121-130 ◽  
Author(s):  
Michael V. Cohen ◽  
James M. Downey
Keyword(s):  
Coronary Artery ◽  
Platelet Reactivity ◽  
Artery Bypass ◽  
Metabolic Activation ◽  
Coronary Intervention ◽  
Myocardial Salvage ◽  
Require Time ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
Oral Agents

Guidelines recommend treatment with a P2Y12 platelet adenosine diphosphate receptor inhibitor in patients undergoing elective or urgent percutaneous coronary intervention (PCI), but the optimal agent or timing of administration is still not clearly specified. The P2Y12 inhibitor was initially used for its platelet anti-aggregatory action to block thrombosis of the recanalized coronary artery or deployed stent. It is now recognized that these agents also offer potent cardioprotection against a reperfusion injury that occurs in the first minutes of reperfusion if platelet aggregation is blocked at the time of reperfusion. But this is difficult to achieve with oral agents which are slowly absorbed and often require time-consuming metabolic activation. Patients with ST-segment elevation myocardial infarction who usually have a large mass of myocardium at risk of infarction seldom have sufficient time for upstream-administered oral agents to achieve a therapeutic P2Y12 level of inhibition by the time of balloon inflation. However, optimal treatment could be assured by initiating an IV cangrelor infusion shortly prior to stenting followed by subsequent post-PCI transition to an oral agent, that is, ticagrelor, once success of the recanalization and absence of need for surgical intervention are confirmed. Not only should this sequence provide optimal protection against infarction, it should also negate bleeding if coronary artery bypass grafting should be required since stopping the cangrelor infusion at any time will quickly restore platelet reactivity. It is anticipated that cangrelor-induced myocardial salvage will help preserve myocardial function and significantly diminish postinfarction heart failure.

Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome

2010 ◽  
Vol 103 (04) ◽  
pp. 774-779 ◽  
Author(s):  
Thomas Cuisset ◽  
Michalis Hamilos ◽  
Leen Delrue ◽  
Corinne Frere ◽  
Katia Verhamme ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Adrenergic Receptor ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Individual Variability ◽  
Platelet Response ◽  
Coronary Syndrome ◽  
Β2 Adrenergic Receptor

SummaryPlatelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet α2A- (α2A-AR) and β2-adrenergic receptor (β2-AR) stimulation. It was the objective of this study to assess the potential influence of α2A-AR and β2-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3/6.7 kb α2A-AR polymorphism, and for Arg16Gly and Gln27Glu β2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 μmol-induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A slight though negligible association was found between 6.3 kb allele of α2A-AR with platelet reactivity ADPAg induced (beta: –2.91 [-5.68;-0.14], p=0.04). A borderline not significant reduction in PRI VASP was observed in 6.3 kb α2A-AR carriers (beta: –3.81 [-0.09;7.72], p=0.06). No significant effect on platelet parameters was observed for the other tested polymorphisms. Common α2A- and β2-adrenergic receptor polymorphisms do not show any major impact on residual platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with 250 mg aspirin and 600 mg clopidogrel is administered.

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.

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

2010 ◽  
Vol 103 (01) ◽  
pp. 213-223 ◽  
Author(s):  
Georgios Sideris ◽  
Remy Cohen ◽  
Catherine Meuleman ◽  
Claire Bal dit Sollier ◽  
Olivier Barthélémy ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Poor Response ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
High Dose ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
To Receive

SummaryCompared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 μM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

Sign in / Sign up

Export Citation Format

Share Document