title: Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events.
abstract: BACKGROUND
  The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation.
  
  
  METHODS
  We conducted this population-based cohort study in western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12-month follow-up, we tracked the use of clopidogrel and CCBs and the rate of MACE (composite of myocardial infarction, ischaemic stroke, stent thrombosis, target lesion revascularization, or cardiac death). We used Cox regression to compute hazard ratios, controlling for potential confounders.
  
  
  RESULTS
  Overall, the 12-month risk for MACE was 14·5%. The rate was 130 per 1000 person years for concomitant clopidogrel and CCB use, 106 for clopidogrel without CCB use, 213 for CCB without clopidogrel use, and 248 for no use of either drug. The adjusted hazard ratio for MACE comparing clopidogrel use with nonuse was 0·52 [95% confidence interval (CI): 0·42-0·64] for CCB users and 0·48 (95% CI: 0·42-0·54) for nonusers, yielding an interaction effect, i.e. relative rate increase, of 1·09 (95% CI: 0·86-1·38). The adjusted hazard ratio for MACE comparing CCB use with nonuse was 1·06 (95% CI: 0·89-1·25) among clopidogrel users.
  
  
  CONCLUSIONS
  Concomitant use of CCBs as a class did not modify the protective effect of clopidogrel and was not associated with increased cardiovascular risk among patients using clopidogrel after coronary stent implantation.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. morten.schmidt@dce.au.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Schmidt
authors.forename: Martin B
authors.initials: MB
authors.lastname: Johansen
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Robertson
authors.forename: Michael
authors.initials: M
authors.lastname: Maeng
authors.forename: Anne
authors.initials: A
authors.lastname: Kaltoft
authors.forename: Lisette O
authors.initials: LO
authors.lastname: Jensen
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Tilsted
authors.forename: Hans E
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000009:adverse effects; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002648:Child; D002675:Child, Preschool; D000077144:Clopidogrel; D015331:Cohort Studies; D003718:Denmark; D004347:Drug Interactions; D015736:Felodipine / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D016016:Proportional Hazards Models; D012306:Risk; D015607:Stents / Q000009:adverse effects; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D014700:Verapamil / Q000009:adverse effects; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D017311:Amlodipine; D000077144:Clopidogrel; D014700:Verapamil; D015736:Felodipine; D013988:Ticlopidine