title: Effect of amlodipine on platelet inhibition by clopidogrel in patients with ischaemic heart disease: a randomised, controlled trial.
abstract: BACKGROUND
  Amlodipine inhibits cytochrome P450 (CYP) enzyme and has the potential to reduce clopidogrel bioactivation in vivo. Reports in previous retrospective studies described greater platelet reactivity in patients on amlodipine.
  
  
  OBJECTIVE
  To evaluate the treatment effect of clopidogrel in patients on amlodipine versus not on calcium-channel blockers (CCBs).
  
  
  METHODS
  Randomised, controlled, open-label trial conducted in a regional acute hospital.
  
  
  METHODS
  98 patients on clopidogrel for ischaemic heart disease were recruited consecutively and randomised to take either amlodipine or drugs with inert CYP effects as controls. The P2Y12 reaction unit (PRU) was measured using whole blood obtained at baseline and on day 28.
  
  
  METHODS
  The primary analysis involved the PRU values on day 28. The secondary analyses were percentage of platelet inhibition and poor response to clopidogrel as defined by PRU>235.
  
  
  RESULTS
  Both groups experienced comparable day 28 PRUs (amlodipine 227±84 vs control 214±90; mean difference 12.7, 95% CI -22 to +47). Percentage of platelet inhibition (amlodipine 33% vs control 38%, mean difference -4.5%, 95% CI -14% to +5%) and those with poor response on day 28 (amlodipine 49% vs control 45%; p=0.76) did not differ significantly.
  
  
  CONCLUSIONS
  Concomitant amlodipine has no negative impact on clopidogrel-mediated platelet inhibition in patients with ischaemic heart disease.
authors.affiliation: Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong, China. liyw@graduate.hku.hk
authors.forename: Andrew Y W
authors.initials: AY
authors.lastname: Li
authors.forename: Fook-Hong
authors.initials: FH
authors.lastname: Ng
authors.forename: Francis K L
authors.initials: FK
authors.lastname: Chan
authors.forename: Prabowo
authors.initials: P
authors.lastname: Tunggal
authors.forename: Kit
authors.initials: K
authors.lastname: Chan
authors.forename: Yuk-Kong
authors.initials: YK
authors.lastname: Lau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006723:Hong Kong; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D017311:Amlodipine; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine