title: Risk of thrombocytopenia with glycoprotein IIb/IIIa inhibitors across drugs and patient populations: a meta-analysis of 29 large placebo-controlled randomized trials.
abstract: OBJECTIVE
  Glycoprotein IIb/IIIa inhibitors (GPIs) reduce myocardial infarction and peri-procedural thrombotic complications in patients undergoing percutaneous coronary intervention (PCI); however, they may cause bleeding and thrombocytopenia, which are associated with poor clinical outcomes. Although the risk of bleeding has been well characterized, the extent of the risk of thrombocytopenia remains uncertain. In this meta-analysis, we aim to evaluate the risk of thrombocytopenia associated with GPI compared with placebo across drugs and patient populations.
  
  
  RESULTS
  Risk ratios were calculated for thrombocytopenia (<100 000 platelets/mm(3)) and severe thrombocytopenia (<50 000 platelets/mm(3)) in 29 randomized large trials (>1000 patients) of GPI vs. placebo involving a total of 123 419 patients. We used meta-analysis techniques to estimate the summary effect across all trials, in pre-specified sub-groups, and in sensitivity analyses to assess the robustness of the data. Glycoprotein IIb/IIIa inhibitor use increases the rate of thrombocytopenia [risk ratio (RR) = 1.62, 95% confidence interval (CI) 1.48-1.78] and severe thrombocytopenia (RR = 3.52, 95% CI 2.87-4.30) compared with placebo. These findings are consistent by route of administration (oral vs. intravenous). Patients with ST-segment elevation myocardial infarction (RR 2.66, 95% CI 2.12-3.34) and elective PCI (RR 2.78, 95% CI 1.76-4.40) treated with a GPI had higher risks of thrombocytopenia than patients with non-ST-segment elevation acute coronary syndrome (RR 1.41, 95% CI 1.25-1.58; P < 0.001 for heterogeneity by sub-group).
  
  
  CONCLUSIONS
  The administration of GPI compared with placebo was associated with a 63% increased risk of thrombocytopenia (<100 000 platelets/mm(3)), and >3-fold increased risk of severe thrombocytopenia (<50 000 platelets/mm(3)). This corresponds to an average of 10-20 additional cases of thrombocytopenia per 1000 patients given GPIs, of which 6-7 cases are severe.
authors.affiliation: Columbia University Medical Center, New York-Presbyterian Hospital, New York, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Wessler
authors.affiliation: Cardiovascular Medicine, Harvard Medical School, Brigham and Women's Hospital, TIMI Study Group, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA rgiugliano@partners.org.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D003324:Coronary Artery Disease / Q000601:surgery*; D014943:Global Health; D006801:Humans; D015994:Incidence; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000009:adverse effects* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate / Q000639:trends; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Glycoprotein IIb/IIIa inhibitor; Meta-analysis; Thrombocytopenia