title: Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes.
abstract: OBJECTIVE
  To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.
  
  
  METHODS
  In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor significantly reduced rates of vascular and total death compared with clopidogrel. In the 905 patients who died postenrolment in the PLATO trial (n=18 624), reviewers, blinded to study treatment, subclassified direct causes of death and evaluated whether infection or bleeding events contributed to fatal events.
  
  
  RESULTS
  Among vascular deaths, there were significantly fewer sudden deaths (63 (0.7%) vs 98 (1.1%), p<0.01) but no significant difference in deaths caused by acute myocardial infarction (179 (1.9%) vs 194 (2.1%), p=0.43) or heart failure (31 (0.3%) vs 42 (0.5%), p=0.20) with ticagrelor compared with clopidogrel. For non-vascular deaths, there was no difference between treatments in deaths directly caused by infection. Although, patients treated with ticagrelor were at lower risk for death where infection was either a direct cause or contributed to death (51 (0.5%) vs 76 (0.8%), HR 0.67 (0.47 to 0.95), p<0.05) but not for bleeding (42 (0.5%) vs 42 (0.5%), HR 0.99 (0.65 to 1.53), p=0.98).
  
  
  CONCLUSIONS
  In this post hoc analysis, ticagrelor compared with clopidogrel reduced total and cardiovascular mortality, which appeared to be mainly mediated by a reduction in sudden death. Importantly, bleeding causing or contributing to death did not differ between treatments.
  
  
  BACKGROUND
  NCT00391872 (http://www.clinicaltrial.gov).
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Christoph
authors: C
authors: Varenhorst
authors: Department of Cardiac and Thoracic Anaesthesia and Surgery, Uppsala University, Uppsala, Sweden.
authors: Ulrica
authors: U
authors: Alström
authors: Department of Cardiology, Lund University, Lund, Sweden.
authors: Oscar Ö
authors: OÖ
authors: Braun
authors: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors: Robert F
authors: RF
authors: Storey
authors: Department of Medicine, Stanford University, Stanford, California, USA.
authors: Kenneth W
authors: KW
authors: Mahaffey
authors: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Maria
authors: M
authors: Bertilsson
authors: TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Christopher P
authors: CP
authors: Cannon
authors: TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Benjamin M
authors: BM
authors: Scirica
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Anders
authors: A
authors: Himmelmann
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Stefan K
authors: SK
authors: James
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Lars
authors: L
authors: Wallentin
authors: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors: Claes
authors: C
authors: Held
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000367:Age Factors; D000368:Aged; D002423:Cause of Death; D000077144:Clopidogrel; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016019:Survival Analysis; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Coronary Artery Disease; Infection