title: Dyspnea and reversibility profile of P2Y₁₂ antagonists: systematic review of new antiplatelet drugs.
abstract: BACKGROUND
  Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Caldeira
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Pinto
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives; D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives; D000077144:Clopidogrel; D004417:Dyspnea / Q000139:chemically induced*; D006801:Humans; D015994:Incidence; D010879:Piperazines / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D052999:Quinazolinones / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D058925:Receptors, Purinergic P2Y12; D013449:Sulfonamides / Q000009:adverse effects; D013876:Thiophenes / Q000009:adverse effects; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D052999:Quinazolinones; D058925:Receptors, Purinergic P2Y12; D013449:Sulfonamides; D013876:Thiophenes; D000249:Adenosine Monophosphate; C117446:cangrelor; C549473:elinogrel; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine