Impact of timing from blood sampling to pharmacodynamic assessment on measures of platelet reactivity in patients treated with P2Y12 receptor inhibitors

2016 ◽  
Vol 116 (12) ◽  
pp. 1060-1069 ◽  
Author(s):  
Fabiana Rollini ◽  
Francesco Franchi ◽  
Kamaldeep Singh ◽  
Jung Cho ◽  
Mona Bhatti ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Time Frame ◽  
Blood Sampling ◽  
Light Transmittance ◽  
P2y12 Inhibitors ◽  
Artery Disease ◽  
A Prospective Study ◽  
The Impact ◽  
Trough Levels ◽  
Over Time

SummarySeveral platelet function tests (PFT) are available to assess the pharmacodynamic (PD) effects of P2Y12 inhibitors. However, there are technical variances between PFT, and P2Y12 inhibitors differ in pharmacological properties. Manufactures of PFT recommend a time-frame within which assessments needs to be executed. However, if the timing from blood sampling to processing affects PD results is unknown. We conducted a prospective study assessing the impact of timing from blood sampling to processing on PD measures using three different PFT. We studied 60 aspirin-treated patients with coronary artery disease (CAD) on maintenance P2Y12 inhibiting therapy [clopidogrel 75 mg/day (n=20), prasugrel 10 mg/day (n=20) and ticagrelor 90 mg bid (n=20)]. PD assessments (trough levels) were performed by VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP) at 30 minutes, 2 and 4 hours post-sampling; VASP was also performed at 24 hours. P2Y12 reaction units (PRU) by VN significantly decreased over time with all P2Y12 inhibitors (clopidogrel p<0.001; prasugrel p=0.016; ticagrelor p<0.001). PRU at 30 minutes and 2 hours were similar, but decreased at 4 hours. LTA showed consistent findings with VN. Conversely, PD measures as assessed by VASP were stable over time (p>0.1 for all P2Y12 inhibitors). In conclusion, in CAD patients on maintenance therapy with P2Y12 inhibitors, timing from blood sampling to processing significantly influences PD measures as assessed by VN and LTA, but not by VASP.

The impact of renal function on platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention with stenting

2014 ◽  
Vol 112 (12) ◽  
pp. 1174-1181 ◽  
Author(s):  
Nicoline Breet ◽  
Corine de Jong ◽  
Willem Jan Bos ◽  
Jochem van Werkum ◽  
Heleen Bouman ◽  
...  
Keyword(s):  
Renal Function ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Light Transmittance ◽  
Clinical Trial Registration ◽  
Platelet Function Test ◽  
Increased Risk ◽  
Function Test ◽  
The Impact

SummaryPatients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease. Previous studies have suggested that patients with CKD have less therapeutic benefit of antiplatelet therapy. However, the relation between renal function and platelet reactivity is still under debate. On-treatment platelet reactivity was determined in parallel by ADP- and AA-induced light transmittance aggregometry (LTA) and the VerifyNow® System (P2Y12 and Aspirin) in 988 patients on dual antiplatelet therapy, undergoing elective coronary stenting. Patients were divided into two groups according to the presence or absence of moderate/severe CKD (GFR<60 ml/min/1.73 m2). Furthermore, the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and stroke at one-year was evaluated. Patients with CKD (n=180) had significantly higher platelet reactivity, regardless of the platelet function test used. Patients with CKD more frequently had high on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) regardless of the platelet function test used. After adjustment for potential confounders, this was no longer significant. The event-rate was the highest in patients with both high on-treatment platelet reactivity (HPR) and CKD compared to those with neither high on-treatment platelet reactivity nor CKD. In conclusion, the magnitude of platelet reactivity as well as the incidence of HPR was higher in patients with CKD. However, since the incidence of HPR was similar after adjustment, a higher rate of co-morbidities in patients with CKD might be the major cause for this observation rather than CKD itself. CKD-patients with HCPR were at the highest risk of long-term cardiovascular events.Clinical Trial Registration: www.clinicaltrials.gov: NCT00352014.

The impact of CYP2C19 genotype on cardiovascular events and platelet reactivity in patients with coronary artery disease receiving clopidogrel

2013 ◽  
Vol 168 (2) ◽  
pp. 1594-1596 ◽  
Author(s):  
Dimitris Tousoulis ◽  
Gerasimos Siasos ◽  
Marina Zaromitidou ◽  
Evangelos Oikonomou ◽  
Konstantinos Maniatis ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Cyp2c19 Genotype ◽  
Artery Disease ◽  
The Impact

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.

Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold

Platelets ◽  
2016 ◽  
Vol 27 (8) ◽  
pp. 777-783 ◽  
Author(s):  
Antonio Tello-Montoliu ◽  
José Rivera ◽  
Diana Hernández-Romero ◽  
Ana Silvente ◽  
Eva Jover ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Platelet Reactivity ◽  
Artery Disease ◽  
Over Time

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)

Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity

2014 ◽  
Vol 112 (12) ◽  
pp. 1198-1208 ◽  
Author(s):  
Yongwhi Park ◽  
Udaya Tantry ◽  
Jong-Hwa Ahn ◽  
Kye Hwan Kim ◽  
Jin-Sin Koh ◽  
...  
Keyword(s):  
Platelet Function ◽  
Platelet Reactivity ◽  
Pde5 Inhibitor ◽  
Light Transmittance ◽  
Reactivity Index ◽  
Double Dose ◽  
High Platelet Reactivity ◽  
Number Of Patients ◽  
The Impact

SummaryAdjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: –2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.

Course of distress, anxiety, and depression in hematological cancer patients: Association between gender and grade of neoplasm

2013 ◽  
Vol 13 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Cristiane Decat Bergerot ◽  
Karen Lynn Clark ◽  
Alexandre Nonino ◽  
Sarah Waliany ◽  
Marco Murilo Buso ◽  
...  
Keyword(s):  
Significant Interaction ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Hospital Anxiety ◽  
Hematological Cancer ◽  
Physical Problems ◽  
Male Patients ◽  
A Prospective Study ◽  
The Impact ◽  
Over Time

AbstractObjective:The aim of our study was to explore the impact of gender and hematological cancer grade on distress, anxiety, and depression in patients receiving chemotherapy.Methods:A prospective study was done in a cohort of 104 patients with hematological cancer. We employed the (1) Distress Thermometer (DT) and the Problem List (PL) and (2) the Hospital Anxiety and Depression Scale (HADS) for assessments at baseline (T1), the halfway timepoint (T2), and completion of chemotherapy (T3).Results:The proportion of patients experiencing significant distress (DT ≥ 4) decreased from the first to the last timepoint; the proportion experiencing anxiety and depression (as assessed by HADS) also decreased. Specifically, 50% of participants reported significant distress levels, 47.1% anxiety, and 26% depression at T1. At T2, the proportion of patients experiencing distress was reduced by 60.8%, by 76% for anxiety, and by 48.5% for depression; at T3, the reduction was close to 80% for all assessments compared with T1. Emotional and physical problems were most commonly reported. Significant reductions were discovered for distress and problem-related distress levels over time, and a significant interaction was found between gender and practical and physical problems (p < 0.05).Significance of results:Our findings suggest that female patients reported more distress, anxiety, and depression than male patients. Gender differences were related to problem-related distress but not to grade of neoplasm. We observed that, over the course of chemotherapy, the distress levels of patients with hematological cancer decrease over time.

Abstract 15044: Impact of Chronic Kidney Disease on the Pharmacodynamic and Pharmacokinetic Effects of Ticagrelor in Patients With Diabetes Mellitus and Coronary Artery Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Naji Maaliki ◽  
Patrick Abou Jaoude ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Chronic Kidney Disease ◽  
Coronary Artery ◽  
Kidney Disease ◽  
Antiplatelet Therapy ◽  
Primary Endpoint ◽  
Platelet Reactivity ◽  
Artery Disease ◽  
Trough Levels

Background: Diabetes mellitus (DM) is a key risk factor for the development of chronic kidney disease (CKD) and patients having both risk factors have increased risk of atherothrombotic events, underscoring the importance of antiplatelet therapy. Ticagrelor reduces ischemic events compared with clopidogrel, with the greatest risk reduction in patients with both DM and CKD. However, how CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor dosing regimens in DM patients is unknown. Methods: This was a prospective, randomized, cross-over study testing the PD/PK profiles of ticagrelor 90mg bid and 60mg bid among DM patients with and without CKD. All patients had coronary artery disease and were on dual antiplatelet therapy with aspirin (81mg qd) and clopidogrel (75mg qd). PD and PK assessments were performed at 3 visits: baseline, after 7-10 days of ticagrelor therapy (pre-crossover; peak and trough), and after 7-10 days of alternative ticagrelor regimen (post-crossover; peak and trough). Results: A total of 92 patients were randomized (CKD-, n=48; CKD+, n=44). Platelet reactivity as assessed by multiple assays (VASP-PRI; VerifyNow P2Y12; LTA) was increased with 60mg compared with 90 mg, which was statistically significant in CKD- but not in CKD+ patients for most PD measures (Figure). Although trough levels of platelet reactivity were numerically lower in CKD+ patients compared with CKD-, there was no significant difference in the pre-defined primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between DM subjects with and without CKD (31±20 vs 25±14; mean difference= 6.4; 95% CI: -1.1 to 14.3; p=0.105; primary endpoint; Figure). PK assessments tracked PD profiles. Conclusions: In patients with DM, platelet inhibition by ticagrelor is similar irrespective of CKD status. However, the PD effects of the 60mg ticagrelor regimen is reduced compared with the 90mg regimen in patients without CKD.

scholarly journals ANTIPLATELET ADEQUACY OF CYCLOPENTYL TRIAZOLOPYRIMIDINE VERSUS CLOPIDOGREL IN-PATIENTS WITH CORONARY HEART DISEASE

2018 ◽  
Vol 11 (12) ◽  
pp. 536
Author(s):  
Feryal Hashim Rada
Keyword(s):  
Platelet Aggregation ◽  
Stable Angina ◽  
Platelet Reactivity ◽  
Stable Coronary Artery Disease ◽  
Light Transmittance ◽  
Reactivity Index ◽  
Major Adverse Cardiovascular Events ◽  
Vasp Phosphorylation ◽  
Coronary Syndromes ◽  
Artery Disease

Objective: Ticagrelor, cyclopentyl triazolopyrimidine drug, and Clopidogrel, second-generation thienopyridine drug are antiplatelet drugs indicated for the prevention of thrombotic events in patients with acute or chronic coronary syndromes. The aim of this study is to assess efficacy and safety outcomes of ticagrelor treatment versus Clopidogrel treatment in patients with stable coronary artery disease (stable angina) using maximal platelet aggregation percent (MPAP) method and platelet reactivity index percent (PRIP) method.Methods: A total of 42 patients (27 male and 15 female), their ages ranging (48±8) years with stable angina enrolled from Ibn Albitar Center for Cardiac Surgery for this crossover study. After satisfying, the properties of inclusion criteria they screened for clopidogrel treatment 75 mg daily for 2 weeks than after 2 weeks periods of wash off they treated with ticagrelor 90 mg twice daily for another 2 weeks. Platelet reactivity was tested at baseline (before treatment), after 2 weeks treatment with clopidogrel and after another 2 weeks treatment with ticagrelor. Platelet reactivity measured by light transmittance aggregometry test and by vasodilator-stimulated phosphoprotein (VASP) phosphorylation test.Results: The results of MPAP after 2 weeks treatment with clopidogrel or ticagrelor showed high significant reduction in platelet aggregation in patients with ticagrelor treatment as compared to clopidogrel treatment (30±6% vs. 44±8%). As well, the results of PRIP using VASP-phosphorylation after 2 weeks treatment with clopidogrel or ticagrelor showed high significant reduction in platelet aggregation in patients with ticagrelor treatment as compared to clopidogrel treatment (22±5% vs. 36±7%).Conclusion: Treatment with ticagrelor produced a reduction in platelet reactivity consistent with the reduction in major adverse cardiovascular events and improved survival without increasing major bleeding.

Sign in / Sign up

Export Citation Format

Share Document