title: The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the PRINC (Plavix Response in Coronary Intervention) trial.
abstract: OBJECTIVE
  This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil.
  
  
  BACKGROUND
  Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week.
  
  
  RESULTS
  Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01).
  
  
  CONCLUSIONS
  In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. patrickg@adhb.govt.nz
authors.forename: Patrick
authors.initials: P
authors.lastname: Gladding
authors.forename: Mark
authors.initials: M
authors.lastname: Webster
authors.forename: Irene
authors.initials: I
authors.lastname: Zeng
authors.forename: Helen
authors.initials: H
authors.lastname: Farrell
authors.forename: Jim
authors.initials: J
authors.lastname: Stewart
authors.forename: Peter
authors.initials: P
authors.lastname: Ruygrok
authors.forename: John
authors.initials: J
authors.lastname: Ormiston
authors.forename: Seif
authors.initials: S
authors.lastname: El-Jack
authors.forename: Guy
authors.initials: G
authors.lastname: Armstrong
authors.forename: Patrick
authors.initials: P
authors.lastname: Kay
authors.forename: Douglas
authors.initials: D
authors.lastname: Scott
authors.forename: Arzu
authors.initials: A
authors.lastname: Gunes
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D015607:Stents; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage
chemical_list: D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D014700:Verapamil; D013988:Ticlopidine