Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome

2016 ◽  
Vol 115 (02) ◽  
pp. 382-391 ◽  
Author(s):  
Jean-Philippe Collet ◽  
Mathieu Kerneis ◽  
Jean-Sebastien Hulot ◽  
Stephen A. O’Connor ◽  
Johanne Silvain ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Absolute Difference ◽  
Function Measurement ◽  
Genetic Profiling ◽  
Coronary Syndrome ◽  
Bedside Test ◽  
Function Testing

SummaryOur aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. “Rapid” (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and “slow” metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU< 30) on prasugrel or high platelet reactivity (> 208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of “rapid” metabolisers on 75 mg of clopidogrel within 30–208 (PRU) of P2Y12 inhibition is non-inferior to “slow” metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of “rapid” and “slow” metabolisers within 30–208 PRU of P2Y12 inhibition was 71 % and 56.9 %, respectively, an absolute difference of +14.1 % (95 % CI, –0.05 % to 28.28 %) with a non-inferiority margin greater than the predefined margin of –10 %. Among patients out of target, all but one “slow” metabolisers displayed low-on prasugrel platelet reactivity while the majority of “rapid” metabolisers (68 %) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30–208 PRU of P2Y12 inhibition was 83.6 % and 79.3 % in “rapid” and “slow” metabolisers, respectively (+4.3 %, 95 % CI –7.3 % to 15.9 %). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.

scholarly journals Impact of smoking habit on platelet reactivity in a cohort of patients admitted due to an acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.C Gomez Polo ◽  
D Vivas Balcones ◽  
A.L Marcano Fernandez ◽  
J Playan Escribano ◽  
L.M Lugo Gavidia ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Smoking Habit ◽  
Tertiary Care ◽  
Funding Source ◽  
P2y12 Inhibitors ◽  
Lower Response ◽  
Coronary Syndrome ◽  
The Impact

Abstract Background Several pharmacodynamic studies have shown the impact of smoking habit on platelet reactivity; with a reduction on platelet aggregation. Wether this inhibition in platelet reactivity is due to tobacco effects in platelet signaling pathways or due to a pharmacodynamic interaction with antiplatelet therapies is not well stablished. Purpose Our aim was to study the influence of smoking habit in platelet reactivity and in the response to P2Y12 inhibitors. Methods Patients admitted in four tertiary care hospitals due to an acute coronary syndrome that undergone percutaneous coronary intervention (PCI) were consecutively and prospectively recruited. All the patients received dual antiplatelet therapy with aspirin and a P2Y12 inhibitor following current European Guidelines. Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12, VASP (Vasodilator-stimulated phosphoprotein) y MEA (Multiple electrode aggregometry). Results A total of 1000 patients were enrolled, of whom 12 had to be excluded due to inaccurate processing of blood samples. 372 patients (37,6%) had smoking habit. Non-smoking patients showed higher prevalence of high blood pressure [423 (68.7%) vs 196 (52.7%)] and diabetes mellitus [213 (34.6%) vs 81 (21.8%)]. Smoking patients were younger [57.3 (9,6) years old vs 68.4 (11.1)], with higher incidence of acute coronary syndrome with ST segment elevation [184 patients (49,5%) vs 241 (39.1%), p&lt;0,001]. There were no differences in platelet function at day 1. When analysing platelet function 30 days post-PCI, a lower inhibition of platelet reactivity in non-smoking patients as compared with smoking patients was observed in those treated with clopidogrel, with higher prevalence of clopidogrel-resistance in non-smoking patients (VerifyNow, 51,2% prevalence of high platelet reactivity in non-smoking patients vs 34,9% 30 days after PCI, p=0,023). On the other hand, smoking patients that received ticagrelor did not show any differences. Patients with smoking habit treated with prasugrel showed a lower response of borderline statistical significance. Conclusion Smoking habit was associated with a lower response to prasugrel of borderline significance, and with higher response to clopidogrel, according with previous studies suggesting a pharmacodynamics interaction between tobacco use and P2Y12 inhibitors. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fondo de Investigaciones Sanitarias (FIS)

Individualised Antiplatelet Therapy – Is There a Role for Platelet Function Testing in Routine Clinical Practice?

2010 ◽  
Vol 5 (1) ◽  
pp. 96 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  
Keyword(s):  
Clinical Practice ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Coronary Intervention ◽  
Platelet Function Testing ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Function Testing

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.

A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients

2014 ◽  
Vol 111 (02) ◽  
pp. 290-299 ◽  
Author(s):  
Ekaterina Lenk ◽  
Niels Straub ◽  
Andreas Beivers ◽  
Daniel Aradi ◽  
Dirk Sibbing
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Adverse Outcomes ◽  
P2y12 Receptor ◽  
Platelet Function Testing ◽  
Coronary Syndrome ◽  
Model Based ◽  
Function Testing ◽  
Model Based Analysis ◽  
Guided Therapy

SummaryAlthough some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incrementalcost- effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

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