ticagrelor and Arrhythmias--Cardiac

Ticagrelor is a new oral antagonist of the platelet P2Y₁₂ receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.

Topics: Adenosine; Animals; Arrhythmias, Cardiac; Evidence-Based Medicine; Heart Failure; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

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

Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel.. We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady- or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months.. Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities.. Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG.

Topics: Acute Coronary Syndrome; Aged; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Clopidogrel; Double-Blind Method; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Ticagrelor

Dyspnea and bradyarrhythmias are frequent adverse effects (AEs) of ticagrelor. AEs commonly occur within the first week of therapy, are dose related and usually mild, but sometimes they may cause drug discontinuation. Currently, the exact mechanisms of ticagrelor-related AEs have not been definitively explained. In addition to the prevalent theory of adenosine overload, other reasonable mechanism like a direct central stimulation hypothesis was suggested. We present a case of incessant Cheyne-Stokes respiration associated with heart rate instability in patient with congestive heart failure and non-ST-segment elevation myocardial infarction, supporting the use of aminophylline as a potential reversal agent of ticagrelor-related AEs.

Topics: Adenosine; Aged; Aminophylline; Arrhythmias, Cardiac; Cardiotonic Agents; Cheyne-Stokes Respiration; Humans; Infusions, Intravenous; Male; Phosphodiesterase Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

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