title: Comparative effect of clopidogrel and aspirin versus aspirin alone on laboratory parameters: a retrospective, observational, cohort study.
abstract: BACKGROUND
  Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Combination therapy of clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in patients in routine clinical practice. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters using a clinical database.
  
  
  METHODS
  We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between November 2004 and April 2011, to identify cohorts of new users (n = 159) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and new users (n = 834) of aspirin alone (100 mg/day). We used a multivariable regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between settings, and compare the mean changes in serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and hematological parameters, including hemoglobin level, hematocrit, and white blood cell (WBC), red blood cell and platelet counts up to two months after the start of study drug administration.
  
  
  RESULTS
  After adjustment, the reduction of WBC count in clopidogrel plus aspirin users was significantly greater than that in aspirin alone users. All other tests showed no statistically significant difference in the mean change from baseline to during the exposure period between clopidogrel plus aspirin users and aspirin alone users. The combination of clopidogrel and aspirin increased the risk of gastrointestinal bleeding compared with aspirin alone, with a relative risk ranging from 2.06 (95% CI, 1.02 to 4.13; p = 0.043) for the multivariate model and 2.61 (95% CI, 1.18 to 5.80; p = 0.0184) for propensity adjustment.
  
  
  CONCLUSIONS
  Our findings suggested that hematological adverse effects may be greater with combination therapy of clopidogrel plus aspirin than with aspirin monotherapy.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Nishida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asai
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006403:Hematologic Tests; D006801:Humans; D007564:Japan; D007962:Leukocytes / Q000187:drug effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057216:Propensity Score; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin