title: The difference in association between aspirin use and other thrombocyte aggregation inhibitors and survival in patients with colorectal cancer.
abstract: Several studies have suggested that the association between aspirin and improved cancer survival is mediated through the mechanism of aspirin as thrombocyte aggregation inhibitors (TAI). The aim of this study was to provide epidemiological evidence for this mechanism assessing the association between overall survival and the use of aspirin and non-aspirin TAI in patients with colorectal cancer.
  
  
  
  In this observational study, data from the Netherlands Comprehensive Cancer Organisation were linked to PHARMO Database Network. Patients using aspirin or aspirin in combination with non-aspirin TAI (dual users) were selected and compared with non-users. The association between overall survival and the use of (non-)aspirin TAI was analysed using Cox regression models with the use of (non-)aspirin TAI as a time-varying covariate.
  
  
  
  In total, 9196 patients were identified with colorectal cancer and 1766 patients used TAI after diagnosis. Non-aspirin TAI were mostly clopidogrel and dipyridamole. Aspirin use was associated with a significant increased overall survival and hazard ratio (HR) 0.41 (95% confidence interval [CI] 0.37-0.47), and the use of non-aspirin TAI was not associated with survival of HR 0.92 (95% CI 0.70-1.22). Dual users did not have an improved overall survival when compared with patients using solely aspirin.
  
  
  
  Aspirin use after diagnosis of colorectal cancer was associated with significantly lower mortality rates and this effect remained significant after adjusting for potential confounders. No additional survival benefit was observed in patients using both aspirin and another TAI.
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Frouws
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Rademaker
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: PHARMO Institute for Drug Outcomes Research, Van Deventerlaan 30/40, 3528 AE, Utrecht, The Netherlands.
authors.forename: M P P
authors.initials: MPP
authors.lastname: van Herk-Sukel
authors.affiliation: Comprehensive Cancer Organisation The Netherlands, P.O. Box 231, 5600 AE, Eindhoven, The Netherlands; Department of Public Health, Erasmus MC Medical Centre, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: V E
authors.initials: VE
authors.lastname: Lemmens
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, The Netherlands.
authors.forename: C J H
authors.initials: CJH
authors.lastname: Van de Velde
authors.affiliation: Department of Medical Oncology, Haga Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands.
authors.forename: J E A
authors.initials: JEA
authors.lastname: Portielje
authors.affiliation: Department of Surgical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, The Netherlands. Electronic address: g.j.liefers@lumc.nl.
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D015179:Colorectal Neoplasms / Q000401:mortality*; D004176:Dipyridamole / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; Clopidogrel; Colorectal neoplasms; Dipyridamole; Platelet aggregation inhibitors