Dyspnea related to reversibly-binding P2Y12 inhibitors: A review of the pathophysiology, clinical presentation and diagnostics

Unverdorben, Martin; Parodi, Guido; Storey, Robert F.

doi:10.1016/j.ijcard.2015.08.162

Cited by 22 publications

(11 citation statements)

References 122 publications

(196 reference statements)

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“…This could be explained by the fact that the adherence to potent P2Y 12 in the continuation group of the TROPICAL-ACS was low due to the high costs of these medications and the side effects (eg, bleeding, dyspnea), which resulted in similar bleeding events. 15 -18…”

Section: Discussionmentioning

confidence: 99%

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

Kheiri

Abdalla

Chahine

et al. 2018

J Cardiovasc Pharmacol Ther

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Aims: Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) are recommended to be placed on potent P2Y12 blockade. However, the long-term bleeding risk is high. Therefore, despite no definitive evidence, switching to clopidogrel beyond the acute phase is common. We aimed to evaluate the clinical outcomes of antiplatelet de-escalation compared with continuation in patients treated with PCI. Methods: We searched databases for randomized clinical trials (RCTs) that evaluated the safety and efficacy of antiplatelet de-escalation compared with continuation in patients treated with PCI. Pooled summary estimates were calculated. Results: We included 3 RCTs with 3391 patients (median follow-up: 12 months). Compared with the continued group, the net clinical outcome (composite of bleeding or thrombotic events) was significantly reduced in the group switched to clopidogrel (8.7% vs 12.1%; risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.43-0.97; P = .03). However, there were similar clinical outcomes between groups for major adverse cardiovascular events (MACE; RR: 0.78; 95% CI: 0.55-1.11; P = .17), all Bleeding Academic Research Consortium (BARC) types bleeding (RR: 0.61; 95% CI: 0.33-1.11; P = .10), or BARC types ≥2 bleeding (RR: 0.49; 95% CI: 0.19-1.26; P = .14). Conclusions: Our results suggest a net clinical benefit of de-escalation therapy shortly after PCI, without increased risk of MACE. Larger randomized trials will be necessary to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

Kheiri

Abdalla

Chahine

et al. 2018

J Cardiovasc Pharmacol Ther

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“…A perturbation in the afferent reflex carried by sensory chemoreceptor, mechanoreceptor or vagal C-fibres from the lungs and respiratory muscles may all contribute to an inappropriate perception of dyspnoea in the sensorimotor cortex of the brain [163]. Two main mechanisms have been proposed to explain how ticagrelor treatment can induce dyspnoea [164]. The first relates to ENT1 antagonism resulting in an elevated concentration of extracellular adenosine, a compound that has been associated with dyspnogenic effects in humans [165].…”

Section: Adverse Effect Profilementioning

confidence: 99%

Ticagrelor: clinical development and future potential

Sanderson¹,

Parker²,

Storey³

2021

Reviews in Cardiovascular Medicine

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“… 63 – 65 Dyspnea is caused by adenosine acting on A1 and A2A receptors present on C fibers of vagal nerve causing bronchoconstriction. 66 Ticagrelor-related dyspnea is described as sudden and unexpected air hunger or unsatisfied inspiration, and in most cases is recognized as mildly intense. 67 The diagnosis of ticagrelor-related dyspnea is based on exclusion of other causes of dyspnea.…”

Section: Mechanism Underlying the Pleiotropic Effects Of Ticagrelormentioning

confidence: 99%

Ticagrelor – toward more efficient platelet inhibition and beyond

Kubisa¹,

Jeżewski²,

Gąsecka³

et al. 2018

TCRM

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Novel antiplatelet drugs, including ticagrelor, are being successively introduced into the therapy of atherothrombotic conditions due to their superiority over a standard combination of clopidogrel with acetylsalicylic acid in patients with acute coronary syndromes (ACS). A P2Y12 receptor antagonist, ticagrelor, is unique among antiplatelet drugs, because ticagrelor inhibits the platelet P2Y12 receptor in a reversible manner, and because it demonstrates a wide palette of advantageous pleiotropic effects associated with the increased concentration of adenosine. The pleiotropic effects of ticagrelor comprise cardioprotection, restoration of the myocardium after an ischemic event, promotion of the release of anticoagulative factors and, eventually, anti-inflammatory effects. Beyond the advantageous effects, the increased concentration of adenosine is responsible for some of ticagrelor’s adverse effects, including dyspnea and bradycardia. Large-scale clinical trials demonstrated that both standard 12-month therapy and long-term use of ticagrelor reduce the risk of cardiovascular events in patients with ACS, but at the expense of a higher risk of major bleeding. Further trials focused on the use of ticagrelor in conditions other than ACS, including ischemic stroke, peripheral artery disease and status after coronary artery bypass grafting. The results of these trials suggest comparable efficacy and safety of ticagrelor and clopidogrel in extra-coronary indications, but firm conclusions are anticipated from currently ongoing studies. Here, we summarize current evidence on the superiority of ticagrelor over other P2Y12 antagonists in ACS, discuss the mechanism underlying the drug–drug interactions and pleiotropic effects of ticagrelor, and present future perspectives of non-coronary indications for ticagrelor.

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Dyspnea related to reversibly-binding P2Y12 inhibitors: A review of the pathophysiology, clinical presentation and diagnostics

Cited by 22 publications

References 122 publications

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

Ticagrelor: clinical development and future potential

Ticagrelor – toward more efficient platelet inhibition and beyond

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Dyspnea related to reversibly-binding P2Y12 inhibitors: A review of the pathophysiology, clinical presentation and diagnostics

Cited by 22 publications

References 122 publications

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials

Ticagrelor: clinical development and future potential

Ticagrelor &ndash; toward more efficient platelet inhibition and beyond

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Product

Resources

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Ticagrelor – toward more efficient platelet inhibition and beyond