prasugrel-hydrochloride and Arrhythmias--Cardiac

Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium.. Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2-7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging.. After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4-950.4] ms for ticagrelor vs. 932.6 [915.5-949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups.. In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping.

Topics: Arrhythmias, Cardiac; Contrast Media; Gadolinium; Humans; Inflammation; Magnetic Resonance Spectroscopy; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

The effects of prasugrel, a third-generation thienopyridine, on myocardial infarction, and ischemia-induced ventricular arrhythmias was evaluated in open-chest anesthetized rats. The role of protein kinase C and phosphoinositide 3-kinase pathways in these effects was also examined.. In the control group, 31.25 ± 3.01% of the risk zone infarcted. At both prasugrel doses, infarct size was significantly smaller than that in the control group: 5.03 ± 0.81% for 3 mg/kg (p < 0.0001), and 8.78 ± 2.04% for 10 mg/kg (p < 0.0001). The protein kinase C antagonist chelerythrine abolished the anti-infarct effect of prasugrel at 24.77 ± 1.73% as did the phosphoinositide 3-kinase antagonist wortmannin abolished the anti-infarct effect of prasugrel at 27.45 ± 2.74%. Ten mg/kg prasugrel reduced the duration of VT (p = 0.0152 vs control), and wortmannin, but not chelerythrine, reversed the effect of prasugrel on arrhythmias (p = 0.0295).. The selective P2Y

Topics: Animals; Arrhythmias, Cardiac; Hemodynamics; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Agonists; Rats; Rats, Wistar; Receptors, Purinergic P2Y12

In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression. The results showed that 19 genes were upregulated in the arrhythmogenic drug-treated cells compared with their expression levels in the non-treated and non-arrhythmogenic drug-treated cells. The arrhythmogenic risks of the drugs were evaluated by scoring gene expression levels. The results indicated that arrhythmogenic risks could be inferred when cells were treated at a concentration 100 times higher than the maximum blood concentration of the drug. Thus, we succeeded in developing a system for evaluation of the arrhythmogenic potential of drugs using gene expression analysis.

Topics: Amlodipine; Arrhythmias, Cardiac; Benzimidazoles; Biphenyl Compounds; Bisoprolol; Cardiotoxicity; Cells, Cultured; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gene Expression Profiling; Gene Expression Regulation; Humans; Induced Pluripotent Stem Cells; Linagliptin; Long QT Syndrome; Myocytes, Cardiac; Naphthalenes; Phenylpropionates; Piperazines; Prasugrel Hydrochloride; Pyridazines; Sumatriptan; Tetrazoles; Transcriptome; Up-Regulation

Topics: Acute Coronary Syndrome; Adenosine; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Therapy, Combination; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Primary percutaneous coronary intervention (PCI) encompassing stent implantation is a mainstay in the management of acute ST-elevation myocardial infarction (STEMI). Despite refinements in techniques and devices, peri- and post-procedural antithrombotic therapy remains pivotal to prevent early and late thrombotic events, without unduly increasing bleeding risk. Concomitant dual antiplatelet therapy with aspirin and clopidogrel has been considered until recently the standard of care in terms of oral antiplatelet agents. However, most recently a novel and more potent thienopyridine, prasugrel, has been tested in randomized trials including patients with STEMI, and subsequently approved for clinical practice in Europe and North America. Despite its potent antithrombotic effect, prasugrel also carries a statistically significant increase in the risk of bleeding, especially in the elderly, those with low body weight, and previous stroke or transient ischemic attack. Thus, the use of prasugrel, as well as that of clopidogrel or ticagrelor, should best be individualized to maximize clinical benefits and minimize hazards.

Topics: Angioplasty, Balloon, Coronary; Arrhythmias, Cardiac; Combined Modality Therapy; Evidence-Based Medicine; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Stents; Thiophenes; Thrombosis