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International audience; BACKGROUND:The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471).METHODS AND RESULTS:A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p

Summary Background Recent studies have suggested that ticagrelor 90 mg twice daily provides stronger platelet inhibition than prasugrel 10 mg once daily in acute coronary syndrome patients undergoing percutaneous coronary intervention. Objectives To compare the effects of ticagrelor 90 mg twice daily and prasugrel 10 mg once daily on platelet reactivity in patients with ST-segment elevation myocardial infarction (STEMI), using: the VerifyNow ® P2Y 12 (VN-P2Y 12 ) assay, expressed in P2Y 12 reaction units (PRU); measurement of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI; %); and light transmission aggregometry (LTA), expressed as residual platelet aggregation (RPA; %). Methods Platelet reactivity was evaluated prospectively using the three assays 30 days after primary PCI in 118 patients with STEMI on a maintenance dose of prasugrel 10 mg once daily ( n = 60) or ticagrelor 90 mg twice daily ( n = 58). Results On-treatment platelet reactivity, assessed by the VN-P2Y 12 assay, was lower for ticagrelor compared with prasugrel (20.91 ± 4.59 PRU vs. 43.50 ± 6.98 PRU; P = 0.008) but was not significantly different when using the more specific VASP-PRI assay (13.05 ± 1.61% vs. 17.44 ± 1.97%; P = 0.09) or RPA assessed by LTA (10.49 ± 1.44% vs. 7.20 ± 1.27%; P = 0.09). Conclusions The difference in platelet reactivity between ticagrelor and prasugrel varies according to the platelet function test in patients with STEMI. The differences observed may be related more to the tests than to the drugs used.

Objectives: This study sought to determine whether red blood cell (RBC) transfusion increases in vivo platelet aggregation and inflammation in coronary and noncoronary patients.Background: RBC tran...

Objectives: This study sought to determine whether the pharmacokinetic (PK) and pharmacodynamic (PD) responses to high or standard clopidogrel loading doses (LDs) differ according to CYP2C19*2 alle...

SummaryThe FXIII-A Leu34 genetic variant increases and accelerates fibrin stabilisation; however, its association with premature coronary artery disease (CAD) and thrombotic events remains controversial. FXIII Val34Leu genotype was determined in 242 young individuals (

The extent of P2Y12 inhibition during coronary intervention is an important determinant of ischemic complications. The currently available oral P2Y12 inhibitors are limited by a relatively slow onset of action and variable on-treatment response.Our objective was to determine the pharmacodynamic (PD) dose-antiplatelet response relationship and the pharmacokinetics of MDCO-157, an intravenous formulation of clopidogrel complexed with sulphobutylether betacyclodextrin, and to identify the dose level of MDCO-157 that matches the PD effect of oral clopidogrel 300 mg.A randomized open-label crossover study was performed in 33 healthy adult volunteers to determine the pharmacokinetic (clopidogrel and clopidogrel H4 thiol active metabolite) and the PD (vasodilator-stimulated phosphoprotein [VASP]) effects of MDCO-157 at doses of 75, 150, and 300 mg and of oral clopidogrel 300 mg.Data are presented as %, mean (standard deviation). The maximum effect of P2Y12 receptor inhibition assessed by flow cytometry using VASP was 70.42 (6.7), 69.45 (7.1), and 65.58 (12.6) for intravenous MDCO-157 at doses of 75, 150, and 300 mg, respectively, compared with 56.6 (17.5) with oral clopidogrel 300 mg administration (p0.0001). Intravenous administration of MDCO-157 led to a stepwise increase in plasma exposure of clopidogrel, higher than with administration of an oral dose of 300 mg (p0.0001). Plasma exposure of H4-thiol also increased with intravenous dose (3.6 ± 2.6, 6.9 ± 4.6, and 12.4 ± 9.1 h·ng/ml for intravenous 75, 150, and 300 mg, respectively) but was lower than with oral administration of a 300-mg dose (34.0 ± 16.0 h.ng/ml; pairwise p0.0001).MDCO-157, an intravenous formulation of clopidogrel complexed with sulphobutylether betacyclodextrin, did not show significant platelet inhibition when administered at doses up to 300 mg. Higher doses with longer infusion may be needed to reach a sufficient threshold of active metabolite generation.ClinicalTrials.gov identifier: NCT01860105.

Aim To explore platelet reactivity on dual antiplatelet therapy (DAPT) of acute coronary syndrome (ACS) patients infected with HIV. Methods and results Acute coronary syndrome patients infected with HIV ( n = 80) were matched to ACS patients without HIV ( n = 160) on age, sex, diabetes, and DAPT (aspirin 100%, clopidogrel 68%, prasugrel 31%, ticagrelor 1%). Platelet reactivity was evaluated after ACS (>30 days) by measuring residual platelet aggregation (RPA) to aspirin and to P2Y12 inhibitors with light transmission aggregometry (LTA), VerifyNow aspirin assay (ARU), and P2Y12 assay (PRU) and with the VASP platelet reactivity index (VASP-PRI). Proportion of patients with high residual platelet reactivity (HPR) was evaluated. HIV-infected ACS patients had higher levels of platelet reactivity in response to P2Y12 inhibitors (RPA: 23.8 ± 2.7% vs. 15.3 ± 1.3%; P = 0.001; PRU: 132 ± 10 vs. 107.4 ± 6.6; P = 0.04; and VASP-PRI: 45.2 ± 2.6% vs. 32.0 ± 2.0%; P

The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (−53.6±48.4 % versus +0.8±53.7 % without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (−81.8 %±24.8 % vs. −72.9 %±32.9 % without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

ObjectivesThis study evaluated the ability of the bedside test Hemochron Jr. Hemonox (International Technidyne Corporation, Edison, New Jersey) to identify patients with insufficient anti-Xa activity level in the catheterization laboratory.BackgroundInadequate anticoagulation in patients undergoing percutaneous coronary intervention (PCI) is associated with increased periprocedural ischemic events.MethodsIn 296 unselected patients undergoing catheterization and/or PCI, whole blood Hemonox clotting time (CT) and activated partial thromboplastin time (aPTT) were measured at baseline (T1) and 10 min after the intravenous administration of enoxaparin (T2) in patients receiving additional enoxaparin and compared with plasma chromogenic anti-Xa activity level.ResultsMedian values were 0.1 IU/ml (interquartile range [IQR]: 0.1 to 0.1 IU/ml) and 0.87 IU/ml (IQR: 0.74 to 1.03 IU/ml) for anti-Xa; 74 s (IQR: 70 to 81 s) and 143 s (IQR: 114 to 206 s) for Hemonox CT; and 44 s (IQR: 39 to 50 s) and 72 s (IQR: 58 to 93 s) for aPTT at T1 and T2, respectively. When using Hemonox CT to discriminate patients with anti-Xa level

High on-treatment platelet reactivity is an independent risk factor of major adverse cardiovascular events following percutaneous coronary intervention or Acute Coronary Syndrome (ACS). HIV-infected patients have a higher risk of recurrent events after ACS than HIV uninfected patients. We

BackgroundInadequate anticoagulation in patients undergoing percutaneous coronary Intervention (PCI) is associated with more frequent periprocedural ischemic events.MethodsWe evaluated the ability of the bedside Hemonox test to identify patients with an anti-Xa activity level out of the therapeutic range in 296 unselected patients undergoing catheterization and/or PCI. Bedside measure of whole blood Hemonox Clotting Time (CT) and activated Partial Prothrombin Time (aPTT) were measured at baseline (T1) and 10’ after the IV administration of enoxaparin (T2) in patients receiving additional enoxaparin and compared to differed plasma chromogenic anti-Xa (AXA) activity measurement.ResultsMedian [IQR] values were 0.1 [0.1-0.1] and 0.87 [0.74-1.03] IU/mL for AXA; 74 [70-81] and 143 [114-206] sec for Hemonox CT, and 44 [39-50] and 72 [58-93] sec for aPTT at T1 and T2 time points, respectively. Hemonox CT strongly correlated with Anti-Xa level spearman r=0.81 (95% CI 0.77-0.84, p