Dataset Information

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel.

ABSTRACT:

Background

Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel.

Objectives

We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel.

Methods

After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61⁺ , CD62p⁺ ), fibrinogen⁺ , phosphatidylserine (PS⁺ ), leukocytes (CD45⁺ ), endothelial cells (CD31⁺ , 146⁺ ), and erythrocytes (CD235a⁺ ) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity.

Results

Concentrations of platelet, fibrinogen⁺ , PS⁺ , leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P ≤ .03). Concentrations of platelet EVs were lower on ticagrelor compared to clopidogrel after 6 months (P = .03). Concentrations of fibrinogen⁺ , PS⁺ , and leukocyte EVs were lower on ticagrelor compared to clopidogrel both after 72 hours and 6 months (P ≤ .03). Concentrations of endothelial EVs and EV procoagulant activity did not differ between patient groups and over time (P ≥ .17).

Conclusions

Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.

SUBMITTER: Gasecka A

PROVIDER: S-EPMC7065161 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel.

Gasecka Aleksandra A Nieuwland Rienk R Budnik Monika M Budnik Monika M Dignat-George Françoise F Eyileten Ceren C Harrison Paul P Lacroix Romaric R Leroyer Aurélie A Opolski Grzegorz G Pluta Kinga K van der Pol Edwin E Postuła Marek M Siljander Pia P Siller-Matula Jolanta M JM Filipiak Krzysztof J KJ

Journal of thrombosis and haemostasis : JTH 20200109 3

<h4>Background</h4>Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel.<h4>Objectives</h4>We compared EV concentrations and EV procoagulant activity ...[more]

PMID: 31833175

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Project description:Importance:The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective:To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants:We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions:Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures:The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results:The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57). Conclusions and Relevance:In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration:clinicaltrials.gov Identifier: NCT02298088.

Project description:BackgroundData are lacking on the effects of the alternation of P2Y12 receptor antagonists (P2Y12) on bleeding and outcome in patients with myocardial infarction (MI) with cardiogenic shock (CS). We compared the effects of different P2Y12 and alternation of P2Y12 (combination) on bleeding and outcome in patients with MI and CS.MethodsData from 247 patients divided into four groups: clopidogrel, ticagrelor, prasugrel, and the combination group, were analyzed. The association between P2Y12 and bleeding as well as 30-day and one-year mortality was examined.ResultsThe highest bleeding rate was observed in patients in the combination group, followed by the clopidogrel, ticagrelor, and prasugrel groups [12(50%) patients, 22(28.2%), 21(18.3%) and 4(13.3%), respectively; p = 0.003]. Bleeding occurred with a similar frequency in the combination and clopidogrel groups (p = 0.081), but more frequently than in the ticagrelor and prasugrel groups (p = 0.002 and p = 0.006, respectively). Bleeding rates were similar in patients receiving P2Y12 alone (p = 0.13). Compared to clopidogrel, both ticagrelor and prasugrel had a lower bleeding risk (aOR: 0.40; 95% CI: 0.18-0.92; p = 0.032 and aOR: 0.20; 95% CI: 0.05-0.85; p = 0.029, respectively) and the combination had a similar bleeding risk (aOR: 2.31; 95% CI: 0.71-7.48; p = 0.16). The ticagrelor and prasugrel groups had more than an 80% and 90% lower bleeding risk than the combination group (aOR: 0.17; 95% CI: 0.06-0.55; p = 0.003 and aOR: 0.09; 95% CI: 0.02-0.44; p = 0.003, respectively). The unadjusted 30-day and one-year mortality were highest in the clopidogrel group, followed by the ticagrelor, prasugrel, and combination groups (44(56.4%) and 55(70.5%) patients died in the clopidogrel group, 53(46.1%) and 56(48.7%) in the ticagrelor group, 12(40%) and 14(46.7%) patients died in the prasugrel, and 6(25%) and 9(37.5%) patients died in the combination group; p = 0.045 and p < 0.0001. After adjustment for confounders, the P2Y12 groups were not independently associated with either 30-day (p = 0.23) or one-year (p = 0.17) mortality risk.ConclusionOur results suggest that the choice of P2Y12 was not associated with treatment outcome. The combination of P2Y12 increased bleeding risk compared with ticagrelor and prasugrel and was comparable to clopidogrel in patients with MI and CS. However, these higher bleeding rates did not result in worse treatment outcomes.

Project description:BackgroundEuropean guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population.MethodsTo compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in the Cardio-STEMI Sanremo registry between February 2011 and June 2013. Cases and controls were defined according to P2Y12 inhibitors, correcting the bias due to lack of randomization by propensity score analysis. Ticagrelor was introduced in 2012 in both in-hospital and pre-hospital settings independently of this study.ResultsOf the 416 patients enrolled in the Cardio-STEMI registry, 401 with a definite diagnosis of STEMI were included in this study. One hundred forty-two patients received ticagrelor and 259 received clopidogrel. Regarding clinical presentation and procedural data, those in the ticagrelor group had lower CRUSADE scores (23 [14-36] vs 27 [18-38]; p = 0.015] but a higher proportion of radial access (33% vs 14%; p < 0.001), percutaneous coronary intervention (PCI; 92% vs 81 %; p = 0.002) and primary PCI ≤ 12 h (82% vs 66%; p = 0.001). The patients in the ticagrelor group had a higher procedural success rate (100% vs. 96%; p = 0.044). There was no difference in Bleeding Academic Research Consortium bleeding and in unadjusted incidence of hospital major adverse cardiovascular events (MACE; cardiac death, myocardial infarction, or stroke) but there was a significant reduction in unadjusted cardiac hospital death in the ticagrelor group (0.7% vs 5.4%; p = 0.024). After correcting for propensity score, hospital death (p = 0.22) and hospital MACE (p = 0.96) did not differ in both groups. The unadjusted survival at 1 year after STEMI was higher in the ticagrelor group (97.8% vs 87.8%; p = 0.024), and this result was confirmed by propensity score analysis (hazard ratio = 0.29 [0.08-0.99]; p = 0.048).ConclusionsIn this real-word propensity score analysis, ticagrelor did not affect the risk of MACE during the hospital phase, or the incidence of hospital bleeding in patients with STEMI. However, in this mono-centric experience, ticagrelor resulted in improved 1-year survival, even after correction by propensity score.

Project description:Background Ticagrelor use during acute coronary syndromes demonstrated a decrease in all-cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non-platelet-derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non-ST-segment-elevation myocardial infarction. Methods and Results In this multicenter, randomized study ( NCT 02244710), patients were considered for inclusion after non-ST-segment-elevation myocardial infarction whenever they were P2Y12-inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28-64), 50 (33-63), and 38 (23-62) cells/mL, respectively, for clopidogrel and 38 (29-60), 45 (32-85), and 35 (24-71) cells/mL, respectively, for ticagrelor ( P=0.6). Endothelial progenitor cell levels were 29 (15-47), 27 (15-33), and 18 (10-25) cells/mL, respectively, for clopidogrel and 20 (11-33), 22 (12-32), and 18 (11-29) cells/mL, respectively, for ticagrelor ( P=0.9). No differences in intraindividual changes were found. Conclusions Patients treated with ticagrelor during non-ST-segment-elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02244710.

Dataset Information

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel.

Background

Objectives

Methods

Results

Conclusions

Publications

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel.

Similar Datasets

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