Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions. Results of a randomized study.
The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n = 20) or 150 mg (n = 20) daily maintenance dose of clopidogrel for 30 days; afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day (52.1 +/- 9% vs. 64.0 +/- 8%; p < 0.001; primary endpoint). The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p < 0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 microM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida College of Medicine-Shands Jacksonville, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Bernardo
Esther
E
Palazuelos
Jorge
J
Desai
Bhaloo
B
Weisberg
Ian
I
Alfonso
Fernando
F
Guzman
Luis A
LA
Hernández-Antolin
Rosana
R
Zenni
Martin Z
MZ
Macaya
Carlos
C
Fernandez-Ortiz
Antonio
A
Bass
Theodore A
TA
D000244:Adenosine Diphosphate; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D012107:Research Design; D013030:Spain; D015607:Stents; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine