METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS—The METAMORPHOSIS Trial

2018 ◽  
Vol 118 (12) ◽  
pp. 2126-2133 ◽  
Author(s):  
Joanna Sikora ◽  
Piotr Niezgoda ◽  
Malwina Barańska ◽  
Katarzyna Buszko ◽  
Natalia Skibińska ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Unstable Angina ◽  
Platelet Reactivity ◽  
Platelet Activity ◽  
Onset Of Action ◽  
P2y12 Inhibitors ◽  
Time Points ◽  
Coronary Syndrome ◽  
Extensive Search ◽  
St Elevation

AbstractExtensive search for methods of overcoming morphine-related delay of the absorption and onset of action of oral P2Y12 inhibitors in patients presenting with acute coronary syndrome is on-going. The aim of the trial was to investigate whether metoclopramide co-administration could reduce this delay and improve the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ticagrelor and its active metabolite AR-C124900XX. Plasma concentration of both compounds and platelet reactivity were evaluated in nine pre-defined time points within 6 hours after administration of ticagrelor loading dose. The results of our study show that mean platelet activity within the first hour was noticeably higher in metoclopramide-naive patients. Moreover, ticagrelor mean plasma concentration was significantly higher within the initial four time points (15, 30, 45, 60 minutes) in patients receiving metoclopramide (p = 0.039; p = 0.009; p = 0.005; p = 0.008, respectively). To conclude, the co-administration of metoclopramide in patients presenting with unstable angina and treated with morphine, has a beneficial effect on the PK/PD profile of ticagrelor and its metabolite; however, its impact on ST-elevation myocardial infarction patients requires further investigation.

scholarly journals Antithrombotic strategy in patients with atrial fibrillation and acute coronary syndrome

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
I Almeida ◽  
H Santos ◽  
M Santos ◽  
H Miranda ◽  
J Chin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Antithrombotic Therapy ◽  
De Novo ◽  
Vitamin K Antagonists ◽  
Antiplatelet Agent ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Short Period ◽  
St Elevation

Abstract Background Atrial fibrillation (AF) is frequent in patients admitted with acute coronary syndromes (ACS). The development of this arrhythmia occurs in 2–21% of patients with non ST-elevation ACS and 21% of ST-elevation ACS. According with the most recent European guidelines, a short period up to 1 week of triple antithrombotic therapy (TAT) is recommended, followed by dual antithrombotic therapy (DAT) using a NOAC and a single antiplatelet agent, preferably clopidogrel. Objective To compare the antithrombotic strategy (DAT vs TAT) used and its prognostic value in patients with AF and ACS. Methods Retrospective analysis of patients' data admitted with ACS in a multicentric registry between 10/2010–09/2019. TAT was defined as the prescription of dual antiplatelet therapy and one anticoagulant and DAT as one antiplatelet and one anticoagulant. Survival and rehospitalization were evaluated through Kaplan-Meier curve. Results 1067 patients were included, mean age 67±14 years, 72.3% male. Patients who developed de novo AF during hospitalization due to ACS were older (75±12 vs 66±14 years, p<0.001) and with higher prevalence of cardiovascular risk factors and cardiovascular disease. AF was more often in patients with ST elevation ACS (53.4%). During hospitalization, AF patients were more often medicated with aspirin, glycoprotein inhibitor, heparin, fondaparinux and vitamin K antagonists. No difference was found regarding P2Y12 inhibitors. AF patients presented more often obstructive coronary disease (normal coronaries 5.4 vs 8.5%, p<0.001) so they were more often submitted to PCI (79.5 vs 70.9%, p<0.001). AF patients presented with higher rates of adverse in-hospital events as re-infarction, heart failure, shock, ventricular arrhythmias, cardiac arrest, stroke, major bleeding and death (p<0.001). At discharge, AF patients were less prescribed with aspirin or ticagrelor, but the rate of clopidogrel prescription was higher, such as vitamin K antagonists or any of the new anticoagulants. In the AF group, 21.5% patients were discharged with TAT and 30.3% with DAT. Concerning patients discharged with TAT, 1-year follow-up revealed no significant differences in mortality (p=0.578), re-admission for cardiovascular causes (p=0.301) and total re-admission rates (p=0.291). Patients discharged with DAT had similar mortality (p=0.623) and re-admission for cardiovascular causes rates (p=0.138), but significant differences were identified regarding total re-admissions (p=0.024). Conclusions In patients with ACS and de novo AF, a low percentage of patients was discharged with oral anticoagulation (51.8%). In those whose anticoagulation was initiated, DAT was the preferred strategy. 1-year outcomes were not different between the antithrombotic strategy, except for all cause re-admission. FUNDunding Acknowledgement Type of funding sources: None.

Effects of oral administration of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine in rat

2020 ◽  
Author(s):  
Xiuling Yang ◽  
Xue Guo ◽  
Li Yanan ◽  
Li Jiaxi ◽  
Liu Yue
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasma Concentration ◽  
Plasma Level ◽  
Adverse Reactions ◽  
Statistical Significance ◽  
Loading Dose ◽  
Time Points ◽  
Coronary Syndrome ◽  
P2y12 Receptor Antagonist ◽  
First Time

Abstract Background: Ticagrelor as a reversible P2Y12 receptor antagonist which plays an important role in the treatment of acute coronary syndrome (ACS). Dyspnea is one of the main adverse reactions of ticagrelor, however the mechanism is not clearly now. The aim of this study was to assess the possible relationship between ticagrelor-related dyspnea and some neurotransmitter in plasma which can contract the bronchial smooth muscle.Methods: The effects of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine was studied in rats. Ticagrelor was administered at a loading dose of 24 mg/kg for the first time, and then maintenance dose 12 mg/kg, twice a day for 6 days. The plasma level of adrenaline, histamine, serotonin, and acetylcholine was determined by LC-MS/MS.Results: The plasma level of serotonin increased after ticagrelor administrating, especially at 1.5h ( p <0.05) reach the level of statistical significance. The level of serotonin in plasma was consistent with ticagrelor blood concentration. Meanwhile, ticagrelor can cause a decrease in the plasma concentration of histamine, and the change was statistically significant at time points of 1.5h, 3.5h and 10.5h respectively. The concentration of the adrenaline and acetylcholine had no change.Conclusions: The results of this study reveal that ticagrelor can increases blood serotonin levels and this may be a cause of dyspnea ticagrelor-related.

Treatment of non-ST elevation acute coronary syndromes

2018 ◽  
Author(s):  
Marco Valgimigli ◽  
Marco Angelillis
Keyword(s):  
Coronary Revascularization ◽  
Artery Bypass ◽  
Treatment Options ◽  
Risk Scores ◽  
Single Individual ◽  
Serious Adverse Events ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
St Elevation

Treatment of patients presenting with a non-ST elevation acute coronary syndrome (NSTE-ACS) aims at immediate relief of ischaemia and the prevention of serious adverse events, including death, myocardial (re)infarction, and life-threatening arrhythmias. In NSTE-ACS, patient management is guided by risk stratification (troponin, electrocardiogram, risk scores, etc.). Treatment options include anti-ischaemic and antithrombotic drugs and coronary revascularization including percutaneous coronary interventions, or coronary artery bypass grafting. While long-term secondary prevention with aspirin monotherapy is currently the gold standard approach for all NSTE-ACS patients who tolerate the drug, additional medications on top of aspirin such as oral P2Y12 inhibitors or oral anticoagulation have been investigated across clinical trials and their long-term use should be guided by the ischaemic versus bleeding risk status of each single individual patient.

P1695Incidence and outcomes of unstable angina compared to non-ST elevation myocardial infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Puelacher ◽  
M Gugala ◽  
P D Adamson ◽  
A S V Shah ◽  
A R Chapmann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Unstable Angina ◽  
High Sensitivity ◽  
Final Diagnosis ◽  
St Elevation Myocardial Infarction ◽  
Cardiovascular Research ◽  
Coronary Syndrome ◽  
All Cause Mortality ◽  
St Elevation ◽  
Heart Foundation

Abstract Objective Assess the incidence and compare characteristics and outcome of unstable angina (UA) and Non-ST-Elevation myocardial infarction (NSTEMI) Design Two independent prospective multicenter diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome (High-STEACS)) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30-days and 1-year. Results 8992 patients were enrolled at 11 centres. UA was adjudicated in 366/4122 (8.9%) and 137/4870 (2.8%) patients in APACE and High-STEACS, respectively, and NSTEMI in 622 (15.1%) and 651 (13.4%). Coronary artery disease was pre-existing in 73% and 76% of patients with unstable angina. At 30-days, all-cause mortality in UA was substantially lower as compared to NSTEMI (0.5% versus 3.7%, p=0.002 in APACE, 0.7% versus 7.4%, p=0.004 in High-STEACS). Similarly, at 1-year in UA all-cause mortality was 3.3% [95% CI 1.2–5.3] vs 10.4% [7.9–12.9] in APACE, and 5.1% [0.7–9.5] vs 22.9% [19.3–26.4] in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, [7.8–14.6] and 7.9%, [5.7–10.2]), and higher than in NCCP (0.6%, [0.2–1.0]). 1-year survival free from future AMI Conclusions The incidence and the mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, British Heart Foundation Project Grants, Butler S

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)

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