Risk of bradyarrhythmia related to ticagrelor: A systematic review and meta-analysis

Pujade, Iris; Perino, Justine; Mathieu, Clément; Arnaud, M; Raschi, Emanuel; Gatti, Milo; Bezin, Julien; Salvo, Francesco

doi:10.1016/j.phrs.2020.105089

Cited by 4 publications

(7 citation statements)

References 60 publications

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“…It can be deduced that TIC prevented the development of electrophysiological abnormalities in SCG neurons after MI by improving the expression of P2Y12 in ganglia and the characteristics of the neuronal ion channel, and it further protected the cardiovascular system and sympathetic nerves. Several studies have shown that TIC is associated with bradycardia, atrioventricular blockage, and ventricular pauses [ 43 , 44 ]. Caution and careful monitoring are required, especially for patients with already compromised conduction systems and/or treated with AV blocking agents [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction

Cheng

Zhan

et al. 2023

JCDD

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Background: The superior cervical ganglion (SCG) plays a key role in cardiovascular diseases. The aim of this study was to determine the changes in the ion channel characteristics of the SCG following myocardial infarction (MI) and the role of pretreatment with the P2Y12 receptor antagonist ticagrelor (TIC). Methods: A total of 18 male rabbits were randomly divided into a control group, MI group, and P2Y12 receptor antagonist (TIC) group (abbreviated as the TIC group). Rabbit MI was performed via two abdominal subcutaneous injections of 150 mg·kg−1·d−1 of isoproterenol (ISO) with an interval of 24 h. TIC pretreatment at 20 mg·kg−1·d−1 was administered via gavage for two consecutive days. The cardiac function of each group was evaluated with echocardiography. ADP receptor P2Y12 expressions in SCGs were determined using RT-PCR and immunofluorescence staining. Ion channel characteristics of SCG neurons were measured using a whole-cell patch clamp. Intracellular calcium concentrations for SCG neurons were measured using confocal microscopy. Results: Cardiac function was reduced in the rabbits of the MI group, the sympathetic nerve activity of SCGs was increased, and the current amplitude of the neuron ion channel was increased. MI led to alterations in the activation and inactivation characteristics of INa channels accompanied by increased expression of P2Y12 in SCGs. Most of these abnormalities were prevented by TIC pretreatment in the TIC group. Conclusions: TIC pretreatment could attenuate the increase in P2Y12 expression in SCGs and the changes to the ion channel characteristics of SCG neurons after MI. This may be the mechanism underlying the cardiac protective effects of TIC.

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Section: Discussionmentioning

confidence: 99%

Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction

Cheng

Zhan

et al. 2023

JCDD

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“…In the disproportionate analysis of SOC levels, ticagrelor focused on cardiac disorders, respiratory disorders, and vascular disorders, which was in high agreement with the PLATO study in which the most common adverse effects in patients were dyspnea and haemorrhage ( Cannon et al, 2010 ). The adverse effect of bradycardia in cardiac disorders has also been a cause of great alarm ( Turgeon et al, 2015 ; Pujade et al, 2020 ). Clopidogrel focused mainly on blood and lymphatic system disorders, vascular disorders, and cardiac disorders, which was also in high agreement with the most common haemorrhage and hematologic abnormalities in the instructions ( Kohriyama et al, 2014 ).…”

Section: Disscussionmentioning

confidence: 99%

“…Ticagrelor was approved for marketing by the U.S. Food and Drug Administration (FDA) on 20 July 2011, and clopidogrel was approved for marketing in June 1998, and ADRs were gradually reported during the clinical application of both drugs. Common adverse effects of ticagrelor include bradycardia and AV block, dyspnea, and risk of bleeding ( Gurbel et al, 2009 ; Goldberg et al, 2015 ; Scirica et al, 2018 ; Pujade et al, 2020 ; Escaned et al, 2021 ). Clopidogrel resistance occurs in approximately 30% of patients ( Tantry et al, 2018 ; Ma et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS

Tang

Wu²,

Xu³

et al. 2022

Front. Pharmacol.

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Background: Ticagrelor and clopidogrel are commonly used antiplatelet agents, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide a reference for safe and reasonable clinical use.Methods: Data were collected in FAERS from 2012 Q1 to 2022 Q2 for data cleaning. We used system organ classes (SOCs) and prefer terms (PTs) from the Medical Dictionary of Regulatory Activity (MedDRA version 25.1). Adverse event reports were retrieved at the PT level. Adverse reaction (ADR) signals of ticagrelor and clopidogrel were mined by calculating reporting odds ratios (ROR), proportional reporting ratios (PRR), information component (IC) and empirical Bayesian geometric mean (EBGM). After that, further analysis of the hemorrhagic signals and their clinical information were performed.Results: The number of ADR reports where the primary suspect (PS) drugs were 15,133 for ticagrelor and 23,860 for clopidogrel. Significant ADR signals were identified by the SOC analysis for ticagrelor including cardiac disorders (ROR 4.87, PRR 4.46), respiratory disorders (ROR 2.45, PRR 2.28), and vascular disorders (ROR 2.22, PRR 2.16). Clopidogrel included blood disorders (ROR 2.86, PRR 2.77), vascular disorders (ROR 2.71, PRR 2.61), and cardiac disorders (ROR 2.29, PRR 2.22). At the PT level, the more frequent ADR signals for ticagrelor were dyspnoea, contusion, and haemorrhage, while clopidogrel were gastrointestinal haemorrhage, anaemia, and drug interaction. The hemorrhagic signals of both were mainly focused on the SOC level of gastrointestinal disorders, injury disorders and vascular disorders and nervous system disorders. The death and life-threatening rate of ticagrelor was 7.76 percentage higher than that of clopidogrel.Conclusion: Clinicians need to pay attention to not only common ADRs but also be alert to new ADR signals when choosing to use ticagrelor and clopidogrel. This study provides a reference for the reasonable and safe clinical use of ticagrelor and clopidogrel.

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“…To date, the risk of bradyarrhythmia in patients treated with ticagrelor is still incompletely evaluated. A meta-analysis showed that ticagrelor increased the risk of bradyarrhythmia or severe bradyarrhythmia; however, due to missing outcome data in two-thirds of eligible studies, the evidence was low to moderate ( Pujade et al, 2020 ). A pharmacovigilance study compared the adverse drug reaction signals of ticagrelor and clopidogrel, but did not summarize ADEs related to arrhythmia ( Tang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for ticagrelor

Pan,

Wang,

Zheng

et al. 2024

Front. Pharmacol.

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Background:Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated.Method:We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name “ticagrelor” published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals.Results:The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for “vascular stent occlusion”. Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor.Conclusion:The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.

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Risk of bradyarrhythmia related to ticagrelor: A systematic review and meta-analysis

Cited by 4 publications

References 60 publications

Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction

Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction

Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for ticagrelor

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