Author + information
- Received May 30, 2008
- Revision received September 16, 2008
- Accepted September 29, 2008
- Published online December 1, 2008.
- Patrick Gladding, FRACP⁎,⁎ (, )
- Mark Webster, FRACP⁎,
- Irene Zeng, MSc⁎,
- Helen Farrell, BHSc⁎,
- Jim Stewart, FRACP⁎,
- Peter Ruygrok, FRACP⁎,
- John Ormiston, FRACP⁎,
- Seif El-Jack, FRACP⁎,
- Guy Armstrong, FRACP⁎,
- Patrick Kay, FRACP⁎,
- Douglas Scott, FRACP⁎,
- Arzu Gunes, MD, PhD† and
- Marja-Liisa Dahl, MD, PhD†
- ↵⁎Reprint requests and correspondence:
Dr. Patrick Gladding, Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92 024, Auckland 1030, New Zealand
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 × 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)
This study was funded in part by the Green Lane Research and Educational Fund and National Heart Foundation of New Zealand. The VerifyNow Platelet function analyzer was provided by Sanofi Aventis, New Zealand. Medication packs and placebo matching were supplied by the Auckland City Hospital Pharmacy, Clinical Trials Unit.
- Received May 30, 2008.
- Revision received September 16, 2008.
- Accepted September 29, 2008.
- American College of Cardiology Foundation