cangrelor and Dyspnea

Oral reversible platelet P2Y12 receptor inhibitors (ticagrelor and elinogrel) cause double-digit rates of dyspnea, while irreversible oral antiplatelet drugs (aspirin, ticlopidoine, clopidogrel, and prasugrel) or intravenous glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, or tirofiban) do not increase the incidence of dyspnea in randomized trials. Dyspnea after oral reversible antiplatelet agents remains unexplained. A transfusion-related acute lung injury (TRALI) hypothesis has been proposed. The dyspnea risks after cangrelor, an intravenous reversible antiplatelet agent, are not well defined but may offer a universal mechanism linking TRALI, dyspnea, and reversible platelet inhibition.. We analyzed safety data from recent head-to-head randomized trials with reversible antiplatelet agents (ticagrelor, elinogrel, and cangrelor) compared to irreversible (clopidogrel/placebo) comparators.. All three reversible antiplatelet agents cause excess dyspnea. In contrast to the high double-digit rates after oral ticagrelor or elinogrel, the dyspnea risks after intravenous cangrelor were smaller (<2%) but still consistently and significantly higher than in the corresponding control arms.. The clinical utility of reversible antiplatelet strategies has been challenged. Despite a potential advantage of fewer bleeding events during heart surgery, reversible antiplatelet agents carry the risk of potential autoimmune reactions manifesting as dyspnea. Repeated binding and unbinding cycles, impaired platelet turnover, and lung sequestration or apoptosis of overloaded destructive platelets are among the potential mechanism(s) responsible for dyspnea after reversible antiplatelet agents.

Topics: Acute Lung Injury; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Dyspnea; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Sulfonamides; Ticagrelor; Ticlopidine; Transfusion Reaction

The dual antiplatelet therapy with acetylsalicylic acid and clopidogrel has been the mainstay of both acute and chronic phase coronary artery disease, reducing importantly the risk of adverse events. Despite a correct compliance, a non-negligible rate of adverse events still happens. New compounds, with improved properties, are now clinically available (such as prasugrel or ticagrelor) or under advanced development. The aim of the present review is the description of these new compounds, particularly prasugrel and ticagrelor.

Topics: Adenosine; Adenosine Monophosphate; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Double-Blind Method; Dyspnea; Hemorrhage; Humans; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Proteinase-Activated; Thiophenes; Ticagrelor; Treatment Outcome

Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.. We aimed to review and quantify the global risk of dyspnea of recent P2Y₁₂ inhibitor drugs, and evaluate its association with the reversibility profile of P2Y₁₂ inhibitors.. A database search (March 2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary outcome was the incidence of dyspnea. Placebo-controlled trials were excluded. Meta-analysis was performed and estimates were expressed as risk ratio (RR) and 95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to the reversibility profile of P2Y₁₂ antagonists.. We found eight RCTs including 41,289 patients. Prasugrel was not associated with an increased risk of dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37-2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57-6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly increased the risk of dyspnea compared with the irreversible inhibitor, prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).. The reversible P2Y₁₂ antagonists ticagrelor, cangrelor, and elinogrel have an increased incidence of dyspnea in increasing order when compared with irreversible P2Y₁₂ inhibitors such as clopidogrel or prasugrel.

Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Dyspnea; Humans; Incidence; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine

Dyspnoea may be induced by some reversibly-binding P2Y

Topics: Adenosine Monophosphate; Aged; Clopidogrel; Coronary Occlusion; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Percutaneous Coronary Intervention; Receptors, Purinergic P2Y12; Survival Analysis; Ticlopidine; Treatment Outcome; Withholding Treatment

Topics: Adenosine Monophosphate; Aged; Anxiety; Chest Pain; Coronary Angiography; Coronary Occlusion; Drug Substitution; Drug-Eluting Stents; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Electrocardiography; Humans; Inferior Wall Myocardial Infarction; Male; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Withholding Treatment