title: Reduction in first and recurrent cardiovascular events with ticagrelor compared with clopidogrel in the PLATO Study.
abstract: BACKGROUND
  We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (e.g., cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events.
  
  
  RESULTS
  In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79-0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70-0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82-0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75-0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non-coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively).
  
  
  CONCLUSIONS
  In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00391872.
authors.affiliation: TIMI Study Group/Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1 floor office, Boston, MA 02115, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Eric
authors.initials: E
authors.lastname: Reyes
authors.forename: Jay
authors.initials: J
authors.lastname: Horrow
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Joao
authors.initials: J
authors.lastname: Morais
authors.forename: José C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Ali
authors.initials: A
authors.lastname: Oto
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D055502:Secondary Prevention; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D013927:Thrombosis / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine