Potential Role of Endogenous Adenosine in Ticagrelor-Induced Dyspnea

Belchikov, Yuly; Koenig, Seth; DiPasquale, Elissa M.

doi:10.1002/phar.1293

Cited by 20 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be that ticagrelor causes an increase in the endogenous adenosine concentration [46, 47] and the inhibition of P2Y 12 on sensory neurons [48]. …”

Section: Discussionmentioning

confidence: 99%

The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis

Tan

Xin²,

Huang

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

ObjectiveIn this study, a systematic evaluation was conducted to estimate the efficacy and safety of ticagrelor for treating acute coronary syndrome (ACS) in general ACS patients and a diabetes mellitus (DM) group.MethodsA search of PubMed, Cochrane Central Register of Controlled Trials, Web of Science, CNKI databases was conducted to analyze relevant randomized controlled trails (RCTs) of ticagrelor treating ACS during 2007 to 2015. Article screening, quality accessing and data extracting was independently undertaken by two reviewers. A meta-analysis was performed to clarify the efficacy and safety of ticagrelor in general ACS patients, and a meta-regression analysis was taken to demonstrate the efficacy and safety of ticagrelor in DM patients compared with general ACS patients.ResultTwenty-two studies with 35004 participants were included. The meta-analysis result implicated that ticagrelor could: 1) reduce the incidence of the composite endpoint [OR = 0.83, 95%CI (0.77, 0.90), P<0.00001] and the incidence of myocardial infarction [OR = 0.81, 95%CI (0.74, 0.89), P = 0.0001]; 2) not statistically reduce the incidence of cardiovascular death, the incidence of stroke and the incidence of bleeding events; 3) increase the incidence of dyspnea [OR = 1.90, 95%CI (1.73, 2.08), P<0.00001] compared with clopidogrel. Meanwhile, compared with prasugrel, ticagrelor could 1) reduce the platelet reactivity of patients at maintenance dose [MD = -44.59, 95%CI (-59.16, -30.02), P<0.00001]; 2) not statistically reduce the incidence of cardiovascular death, the platelet reactivity of patients 6 hours or 8 hours after administration, or the incidence of bleeding events; 3) induce the incidence of dyspnea [OR = 13.99, 95%CI (2.58, 75.92), P = 0.002]. Furthermore, the result of meta-regression analysis implicated that there was a positive correlation between DM patients and the platelet reactivity of patients 6 hours and 8 hours after administration, but there was no obvious correlation between DM patients and general ACS patients in other endpoints.ConclusionTicagrelor could reduce the incidence of composite endpoint of cardiovascular death, myocardial infarction and stroke as well as platelet reactivity in DM patients with ACS, while not increasing the risk of bleeding. Because there are differences in platelet reactivity between DM patients and general ACS patients, we suggest that caution is needed when using ticagrelor in clinical applications.

show abstract

“…It may be that ticagrelor causes an increase in the endogenous adenosine concentration [46, 47] and the inhibition of P2Y 12 on sensory neurons [48]. …”

Section: Discussionmentioning

confidence: 99%

The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis

Tan

Xin²,

Huang

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Ticagrelor inhibits platelet activity via P2Y 12 receptor inhibition and also via adenosine [ 35 ]. A potential mechanism of ticagrelor-induced dyspnoea involves increased endogenous levels of adenosine [ 36 ]. Adenosine can induce dyspnoea in normal [ 37 ] and asthmatic [ 38 ] subjects.…”

Section: Ticagrelor Pharmacokinetic Profilementioning

confidence: 99%

Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update

Teng

2015

Clin Pharmacokinet

116

View full text Add to dashboard Cite

Despite advancements in treatments for acute coronary syndromes over the last 10 years, they continue to be life-threatening disorders. Currently, the standard of treatment includes dual antiplatelet therapy consisting of aspirin plus a P2Y12 receptor antagonist. The thienopyridine class of P2Y12 receptor antagonists, clopidogrel and prasugrel, have demonstrated efficacy. However, their use is associated with several limitations, including the need for metabolic activation and irreversible P2Y12 receptor binding causing prolonged recovery of platelet function. In addition, response to clopidogrel is variable and efficacy is reduced in patients with certain genotypes. Although prasugrel is a more consistent inhibitor of platelet aggregation than clopidogrel, it is associated with an increased risk of life-threatening and fatal bleeding. Ticagrelor is an oral antiplatelet agent of the cyclopentyltriazolopyrimidine class and also acts through the P2Y12 receptor. In contrast to clopidogrel and prasugrel, ticagrelor does not require metabolic activation and binds rapidly and reversibly to the P2Y12 receptor. In light of new data, this review provides an update on the pharmacokinetic, pharmacodynamic and pharmacogenetic profiles of ticagrelor in different study populations. Recent studies report that no dose adjustment for ticagrelor is required on the basis of age, gender, ethnicity, severe renal impairment or mild hepatic impairment. The non-P2Y12 actions of ticagrelor are reviewed, showing indirect positive effects on cellular adenosine concentration and biological activity, by inhibition of equilibrative nucleoside transporter-1 independently of the P2Y12 receptor. CYP2C19 and ABCB1 genotypes do not appear to influence ticagrelor pharmacodynamics. A summary of drug interactions is also presented.

show abstract

“…Various side effects have been reported for both clopidogrel (bleeding, liver and bone injury, enhanced lipopolysaccharide-induced inflammation) [365,366] and ticagrelor (bleeding, dyspnoea) [367]. In more recent reports, it was suggested that there may be a role for endogenous adenosine in ticagrelor-induced dyspnoea [368,369].…”

Section: Thrombosismentioning

confidence: 99%

Blood cells: an historical account of the roles of purinergic signalling

Burnstock

2015

Purinergic Signalling

View full text Add to dashboard Cite

The involvement of purinergic signalling in the physiology of erythrocytes, platelets and leukocytes was recognised early. The release of ATP and the expression of purinoceptors and ectonucleotidases on erythrocytes in health and disease are reviewed. The release of ATP and ADP from platelets and the expression and roles of P1, P2Y 1 , P2Y 12 and P2X1 receptors on platelets are described. P2Y 1 and P2X1 receptors mediate changes in platelet shape, while P2Y 12 receptors mediate platelet aggregation. The changes in the role of purinergic signalling in a variety of disease conditions are considered. The successful use of P2Y 12 receptor antagonists, such as clopidogrel and ticagrelor, for the treatment of thrombosis, myocardial infarction and stroke is discussed.

show abstract

Potential Role of Endogenous Adenosine in Ticagrelor-Induced Dyspnea

Cited by 20 publications

References 29 publications

The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis

The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis

Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update

Blood cells: an historical account of the roles of purinergic signalling

Contact Info

Product

Resources

About