title: The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.
abstract: Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy.
  
  
  
  A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved.
  
  
  
  The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97).
  
  
  
  Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence.
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Leader
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Israel; Department of Medicine A, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Ravit
authors.initials: R
authors.lastname: Zelikson-Saporta
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Israel; Department of Cardiology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Pereg
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Spectre
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovski
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Israel; Department of Family Medicine, Sharon-Shomron District, Clalit Health Services, Netanya, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Hermoni
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Israel; Department of Medicine A, Meir Medical Center, Kfar Saba, Israel. Electronic address: michael2@clalit.org.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Lishner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Antiplatelet; Aspirin; Cancer; Clopidogrel