title: Relationship between changes in platelet reactivity and ischemic events following percutaneous coronary intervention: a meta-regression analysis of 30 randomized trials.
abstract: OBJECTIVE
  High on-treatment platelet reactivity (HPR) is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). However, whether reducing platelet reactivity can lead to a lower incidence of ischemic events after PCI is still controversial. Therefore, we sought to investigate this issue by a meta-regression analysis of randomized trials.
  
  
  METHODS
  We collected randomized trials reporting HPR rates in patients receiving different antiplatelet therapies. ΔHPR was defined as the difference between HPR rates achieved in control vs. experimental arms, and the relationship between ΔHPR and clinical outcomes was evaluated.
  
  
  RESULTS
  Thirty trials totalling 6683 patients with a mean follow-up of 3-month were included. Reducing platelet reactivity was associated to a decreased risk of major adverse cardiac events (MACE), with a linear relationship between ΔHPR and MACE (change in tau(2) = -2.50; p = 0.023). Particularly, achieving a 10% difference in HPR rates resulted in a parallel risk reduction in MACE of about 11% (Exp((b)) = 0.98; 95% CI, 0.97-0.99). Changes in HPR predict the risk of ischemic events in patients with acute coronary syndrome (change in tau(2) = -2.52; Exp((b)) = 0.98; 95% CI, 0.97-0.99; p = 0.03), but not in patients with poor response to clopidogrel (change in tau(2) = -1.44; Exp((b)) = 0.98; 95% CI, 0.96-1.01; p = 0.19) or stable coronary artery disease (change in tau(2) = -0.14; Exp((b)) = 0.99; 95% CI, 0.94-1.05; p = 0.89).
  
  
  CONCLUSIONS
  Reducing HPR occurrence decreases the risk of ischemic events in patients with acute coronary syndrome undergoing PCI, whereas a strategy of reducing platelet reactivity does not improve clinical outcomes in patients with poor response to clopidogrel or stable coronary artery disease.
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Piccolo
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy. Electronic address: gengalas@unina.it.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Galasso
authors.affiliation: Division of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Parodi
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Antoniucci
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Piscione
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D006801:Humans; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology*; D062645:Percutaneous Coronary Intervention; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012307:Risk Factors
keywords: Antiplatelet therapy; Meta-regression; P2Y12 inhibitors; Percutaneous coronary intervention; Platelet reactivity