Comparison between hirudin and citrate in monitoring the inhibitory effects of P2Y12 receptor antagonists with different platelet function tests

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)

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Aspirin - resistance? A few critical considerations on definition, terminology, diagnosis, clinical value, natural course of atherosclerotic disease, and therapeutic consequences

VASA ◽

10.1024/0301-1526/a000145 ◽

2011 ◽

Vol 40 (6) ◽

pp. 429-438 ◽

Cited By ~ 8

Author(s):

Berent ◽

Sinzinger

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Aspirin Resistance ◽

Point Of View ◽

Evidence Based ◽

Platelet Function Tests ◽

Clinical Value ◽

Vascular Events ◽

Therapeutic Consequences ◽

Function Tests

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.

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Faculty Opinions recommendation of Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726356134.793518643 ◽

2016 ◽

Author(s):

Davide Cattano

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Antiplatelet Drugs ◽

Platelet Function Tests ◽

Function Tests

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LACK OF CORRELATION BETWEEN INTRAPLATELET cAMP INCREASE AND SYSTEMIC CIRCULATORY EFFECTS

10.1055/s-0038-1644532 ◽

1987 ◽

Author(s):

W Haarmann ◽

H Weisenberger

Keyword(s):

Platelet Function ◽

Circulatory System ◽

Human Platelets ◽

Platelet Function Tests ◽

Inotropic Effects ◽

Circulatory Effects ◽

Function Tests ◽

Drug Concentrations ◽

Camp Metabolism ◽

The Difference

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.

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