The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel: The PRINC (Plavix Response in Coronary Intervention) Trial

JACC Cardiovasc Interv. 2008 Dec;1(6):612-9. doi: 10.1016/j.jcin.2008.09.005.

Abstract

Objectives: 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).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Angioplasty, Balloon, Coronary* / instrumentation
  • Calcium Channel Blockers / administration & dosage
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Interactions
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Stents
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Verapamil / administration & dosage

Substances

  • Calcium Channel Blockers
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Verapamil
  • Ticlopidine