title: Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.
abstract: BACKGROUND
  Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.
  
  
  RESULTS
  Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant.
  
  
  CONCLUSIONS
  In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.
  
  
  BACKGROUND
  URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.
authors.affiliation: Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden. Stefan.james@ucr.uu.se
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Philip
authors.initials: P
authors.lastname: Aylward
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Buck
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Jay
authors.initials: J
authors.lastname: Horrow
authors.forename: Hugo
authors.initials: H
authors.lastname: Katus
authors.forename: Matyas
authors.initials: M
authors.lastname: Keltai
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Keyur
authors.initials: K
authors.lastname: Parikh
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Karolina
authors.initials: K
authors.lastname: Szummer
authors.forename: Daniel
authors.initials: D
authors.lastname: Wojdyla
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D002908:Chronic Disease; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine