ABSTRACT
Usefulness of higher (>300 mg) loading doses of clopidogrel has been demonstrated in studies from the United States and Europe. The present study evaluated platelet aggregation after the administration of a 450-mg loading dose of clopidogrel in Japanese patients undergoing coronary stenting. Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 450-mg clopidogrel loading in 25 patients undergoing coronary stenting. Platelets were stimulated with 5 and 20 micromol/l adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Platelet aggregation (5 micromol/l ADP 42.8% +/- 13.5% and 20 micromol/l ADP 51.2% +/- 11.6%) was significantly suppressed Subject(s)
Angioplasty, Balloon, Coronary/instrumentation
, Asian People
, Coronary Artery Disease/therapy
, Platelet Aggregation Inhibitors/administration & dosage
, Platelet Aggregation/drug effects
, Stents
, Ticlopidine/analogs & derivatives
, Adenosine Diphosphate
, Aged
, Clopidogrel
, Coronary Artery Disease/blood
, Coronary Artery Disease/drug therapy
, Coronary Artery Disease/ethnology
, Female
, Hemorrhage/chemically induced
, Humans
, Japan
, Male
, Middle Aged
, Platelet Aggregation Inhibitors/adverse effects
, Ticlopidine/administration & dosage
, Ticlopidine/adverse effects
, Time Factors
, Treatment Outcome
ABSTRACT
In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 mumol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% +/- 11% vs 38% +/- 15%, not significant) and 20 mumol/l adenosine diphosphate (48% +/- 13% vs 51% +/- 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.
Subject(s)
Angioplasty, Balloon, Coronary , Coronary Artery Disease/therapy , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/drug effects , Thrombosis/prevention & control , Ticlopidine/analogs & derivatives , Ticlopidine/administration & dosage , Adenosine Diphosphate , Aged , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/instrumentation , Asian People , Clopidogrel , Coronary Artery Disease/blood , Coronary Artery Disease/ethnology , Dose-Response Relationship, Drug , Female , Humans , Japan , Male , Middle Aged , Pilot Projects , Stents , Thrombosis/blood , Thrombosis/etiology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The loading dose of ticlopidine is 500 mg in both the US and Europe and 200 mg in Japan. A lower loading dose of clopidogrel might achieve adequate platelet inhibition in Japanese patients. METHODS AND RESULTS: Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 150-mg (n=20) and 300-mg (n=20) clopidogrel loading. Platelets were stimulated with 5 and 20 micromol/L adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Pretreatment ADP-induced platelet aggregation in the 150-mg clopidogrel group did not differ from that of the 300-mg group. The administration of 300-mg clopidogrel loading dose resulted in lower platelet aggregation 2 h after the administration (5 micromol/L ADP: 53+/-9% vs 61+/-12%, p<0.05 and 20 micromol/L ADP: 61+/-10% vs 68+/-9%, p<0.05). A lower platelet aggregation induced with 20 micromol/L ADP was still observed 4 h after the 300-mg clopidogrel loading (58+/-10% vs 65+/-9%, p<0.05). CONCLUSIONS: The 150-mg clopidogrel loading does not achieve rapid platelet inhibition. The 300-mg loading dose should be used to suppress platelet function rapidly even in Japanese patients undergoing coronary stent placement.