Variable responsiveness to clopidogrel and aspirin among patients with acute coronary syndrome as assessed by platelet function tests

2008 ◽  
Vol 122 (3) ◽  
pp. 336-345 ◽  
Author(s):  
Boris Shenkman ◽  
Shlomi Matetzky ◽  
Paul Fefer ◽  
Hanoch Hod ◽  
Yulia Einav ◽  
...  
Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Manuel Mayr ◽  
Dorothee Kaudewitz ◽  
Philipp Skroblin ◽  
Peter Willeit ◽  
Anna Zampetaki ◽  
...  

Introduction: Platelets contribute plasma microRNAs (miRNAs). Levels of platelet-related miRNAs change in plasma in response to platelet inhibition. Hypothesis: It is currently unclear how plasma miRNAs correlate to platelet function in patients with acute coronary syndrome (ACS). Methods: We measured plasma miRNAs in 125 patients with a history of ACS (STEMI, NSTEMI or unstable angina) who have undergone detailed assessment of platelet function 30 days after the acute event. Results: Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in patients on different anti-platelet therapies (clopidogrel, prasugrel, aspirin). Key platelet-related miRNAs were correlated with platelet function tests, including optical aggregometry using the agonists ADP and arachidonic acid, VerifyNow P2Y12 assay and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. Significant associations were obtained for miR-126 with the VerifyNow (rp=0.347, n=39, P=0.033) and VASP assay (rp=0.224, n=125, P=0.013). Other abundant platelet miRNAs also showed strong correlations with the VASP assay: miR-223 (rp =0.231, P=0.003), miR-191 (rp =0.243, P=0.007), miR-24 (rp =0.246, P=0.006), miR-197 (rp=0.293, P=0.008), miR-30b (rp=0.230, P=0.010) and miR-20b (rp=0.231 , P=0.010). Conclusions: Levels of platelet-related plasma miRNAs correlate with platelet function tests in ACS patients. Our findings reinforce the concept that platelets are an important contributor to the plasma miRNA pool.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.H Kim ◽  
C.D Jin ◽  
K Song ◽  
G.M Lee ◽  
H.Y Moon ◽  
...  

Abstract Background East Asians treated with potent P2Y12 inhibitors, prasugrel or ticagrelor exhibit more potent platelet inhibition than clopidogrel. Whether half-dose de-escalation strategy would improve optimal platelet reactivity at maintenance in East Asian patients with acute coronary syndrome (ACS) remains uncertain. Method In de-escalation strategy single center study, eligible Korean ACS patients (n=96) were assigned to receive standard-dose ticagrelor (n=33), prasugrel (n=28), followed by half-dose reduction at 1 month for maintenance, and clopidogrel (n=35) as control. Platelet reactivity was measured by VerifyNow, light transmittance aggregometry (LTA) and multiple electrode aggregometry (MEA). The investigators aim to compare optimal platelet reactivity status (OPR, defined as 85–208 P2Y12 reaction unit [PRU] for VerifyNow (VN), 16%–47% for LTA and 19–46 U for MEA) among 3 different platelet function tests at 3 months post PCI. Results At 3 months, ticagrelor achieved significantly lower PRU (17 [6–51] vs. 95 [61–151] vs. 172 [111–204]) than prasugrel and clopidogrel, resulting OPR rate 10% vs. 57.7% vs. 60.0%, respectively. Similar results were observed at LTA method (2% [0–12] in ticagrelor vs. 18% [13–22] in prasugrel vs. 18% [11–30] in clopidogrel), with OPR rate 11.8% vs. 69.2% vs. 50.0%, respectively. However, platelet reactivity was similar by MEA method (16 [13–20] in ticagrelor vs. 17 [13–22] in prasugrel vs. 19 [14–28] in clopidogrel), with OPR rate 33.3% vs. 40.0% vs. 42.0%, respectively (all p>0.005). Among the three tests, resulting higher correlation between VN and LTA (r=0.745), MEA and LTA vs. MEA and VN showed lower correlations (r=0.412 and r=0.303). (Fig.) Conclusion In Korean ACS patients with half-dose de-escalation strategy after 1 month, OPR rate in ticagrelor is still rare during 3-month treatment by VN and LTA methods, however, prasugrel appears comparable to clopidogrel. VN/LTA might overestimate platelet function than MEA or MEA underestimate OPR rate than VN/LTA. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Playan Escribano ◽  
D Vivas Balcones ◽  
L.M Lugo Gavidia ◽  
J.C Gomez Polo ◽  
A.L Marcano Fernandez ◽  
...  

Abstract Background Different “ex vivo” studies have shown both a greater platelet activation and higher rates of resistance to clopidogrel in obese patients. Although there is less evidence, less prasugrel activity has also been observed in these patients. Our aim was to study the variability of the response to clopidogrel, ticagrelor and prasugrel in obese patients, defined as a body mass index ≥30. Methods Prospective, multicenter, observational, pharmacodynamic study, conducted in a Spanish population of patients with an acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and double anti-aggregation with acetylsalicylic acid and a P2Y12 receptor inhibitor. Platelet function tests were performed the morning after the ICP and 30 days after it, including: 1) VerifyNow P2Y12 assay; 2) multiple electrode aggreometry (Multiplate); and 3) VASP analysis. Results Of the total patients included (988), 300 were obese (30.3%). The obese group was younger (62.8±12 years vs 64.9±12), had a higher incidence of arterial hypertension (76.3% vs. 56.7%), diabetes mellitus (35% vs. 27.5%); and lower incidence of chronic kidney disease (7.7% vs. 17%). There were no differences in the acute phase (day 1 after PCI) in the pharmacodynamic response to any of the P2Y12 inhibitors used. After 30 days, greater platelet aggregation (decreased response) was documented in obese patients treated with prasugrel according to VASP tests (PRI in non-obese 23.9±13% vs. 30.4±14.7% in obese, p 0.035) and MEA (area under the aggregation units curve in non-obese 251.7±104.1 vs 320±166.7 in obese, p 0.007) and a numerical trend with VerifyNow. A trend in the same direction was also observed in patients treated with clopidogrel that did not reach statistical significance with all the platelet function tests used. No differences were observed in the ticagrelor group. Conclusion Obese patients with an ACS treated with PCI have a worse response to thienopyridines than non-obese patients in the maintenance phase of antiaggregant treatment, while the response to ticagrelor is not affected by obesity. Completing the clinical follow-up proposed by the registry is necessary to know if these differences have an implication in cardiovascular events. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fondo de Investigaciones Sanitarias (FIS)


2020 ◽  
Vol 9 (1) ◽  
pp. 194 ◽  
Author(s):  
Pierre Fontana ◽  
Marco Roffi ◽  
Jean-Luc Reny

In the field of antithrombotics, precision medicine is of particular interest, as it may lower the incidence of potentially life-threatening side effects. Indeed, antiplatelet drugs such as P2Y12 inhibitors are one of the most common causes of emergency admissions for drug-related adverse events. The last ten years have seen a continuous debate on whether platelet function tests (PFTs) should be used to tailor antiplatelet drugs to cardiovascular patients. Large-scale randomized studies investigating the escalation of antiplatelet therapies according to the results of PFTs were mostly negative. Potent P2Y12 inhibitors are recommended as a first-line treatment in acute coronary syndrome patients, bringing the bleeding risk at the forefront. De-escalation from prasugrel or ticagrelor to clopidogrel is now considered, with or without the use of a PFT. This review covers recent advances in escalation and de-escalation strategies based on PFTs in various clinical settings. It also describes the main features of the most popular platelet function tests as well as the potential added value of genetic testing. Finally, we detail practical suggestions on how PFTs could be used in clinical practice.


VASA ◽  
2011 ◽  
Vol 40 (6) ◽  
pp. 429-438 ◽  
Author(s):  
Berent ◽  
Sinzinger

Based upon various platelet function tests and the fact that patients experience vascular events despite taking acetylsalicylic acid (ASA or aspirin), it has been suggested that patients may become resistant to the action of this pharmacological compound. However, the term “aspirin resistance” was created almost two decades ago but is still not defined. Platelet function tests are not standardized, providing conflicting information and cut-off values are arbitrarily set. Intertest comparison reveals low agreement. Even point of care tests have been introduced before appropriate validation. Inflammation may activate platelets, co-medication(s) may interfere significantly with aspirin action on platelets. Platelet function and Cox-inhibition are only some of the effects of aspirin on haemostatic regulation. One single test is not reliable to identify an altered response. Therefore, it may be more appropriate to speak about “treatment failure” to aspirin therapy than using the term “aspirin resistance”. There is no evidence based justification from either the laboratory or the clinical point of view for platelet function testing in patients taking aspirin as well as from an economic standpoint. Until evidence based data from controlled studies will be available the term “aspirin resistance” should not be further used. A more robust monitoring of factors resulting in cardiovascular events such as inflammation is recommended.


PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40641 ◽  
Author(s):  
Shuang Zhang ◽  
Jing Yuan ◽  
Miao Yu ◽  
Hong Fan ◽  
Zhang-Qiang Guo ◽  
...  

1987 ◽  
Author(s):  
W Haarmann ◽  
H Weisenberger

Compounds inhibiting platelet function by acting on platelet cAMP metabolism usually also have effects on the circulatory system, i.e. they decrease systemic blood pressure (bp) and are positive inotropic. For several compounds selected because of their distinct platelet inhibitory effects, the influence on these parameters in animals and on the cAMP metabolism in human platelets was determined.Inotropic effects and bp were measured via an indwelling catheter in anestetised cats after i.v. application of the test compounds. The inhibition of platelet PDEs was measured in freeze-thaw homogenates of human platelets using 3H-cAMP as substrate. Intraplatelet cAMP changes were measured by prelabelling the ATP pool with 3H-adenine and isolation of 3H-cAMP. Linear regression analysis of the drug concentrations causing a doubling of intraplatelet cAMP levis and the % difference in bp or the % difference in dp/dt, resp., by i.v. application of 0.3 mg/kg test compound yielded the following results:cAMP vs % diff. bp : r=0.02, N=18cAMP vs % diff. dp/dt: r = 0.02 , N = 15In contrast to a good correlation between intraplatelet cAMP levels and inhibition of platelet function tests, no obvious relationship was seen between cAMP and decrease in bp and positive initropic effects. It is not known whether the lack of correlation could be due to a different drug access to platelets and the bp regulatory system.A biochemical parameter, i.e. intraplatelet cAMP increase by inhibition of PDEs correlates reasonably well with the inhibition of platelet function tests. This parameter is not useful, however, to predict the effects on the heart and the circulatory system.


1981 ◽  
Vol 11 (2) ◽  
pp. 183-203 ◽  
Author(s):  
Pamela R. Roper-Drewinko ◽  
Benjamin Drewinko ◽  
Gail Corrigan ◽  
Dennis Johnston ◽  
Kenneth B. McCredie ◽  
...  

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