Impact of high loading and maintenance dose of clopidogrel within the first 15 days after percutaneous coronary intervention on patient outcome.
BACKGROUND
An increase in clopidogrel dose results in an improved inhibition of platelet aggregation. However, whether an increase in clopidogrel dose may improve patient outcome is still debated. The aim of this study was to analyze the impact on patient outcome of an increase in clopidogrel loading and maintenance doses within the first 15 days after percutaneous coronary intervention (PCI).


METHODS
Between 2003 and 2007, we included 2,954 consecutive patients who underwent PCI and stent implantation. We compared 2 historical groups. In the "low-dose" group (2003-2005, n = 1,984), patients were pretreated with a 300-mg clopidogrel loading dose followed by 75 mg/d after PCI. In the "high-dose" group (2006-2007, n = 970), patients were pretreated with a 600-mg clopidogrel loading dose followed by 150 mg/d within the first 15 days and 75 mg/d thereafter. The composite primary end point (death, myocardial infarction, stent thrombosis) and bleeding were systematically indexed during the 2-month follow-up period.


RESULTS
Clinical and most of angiographic characteristics were similar between the 2 groups. By multivariate analysis, high dose of clopidogrel was associated with a decrease in the composite primary end point (hazard ratio 0.694, 95% CI 0.485-0.993, P = .046). The other predictors were age, left ventricular ejection fraction, diabetes, renal failure, and acute coronary syndrome. Major bleeding was similar in the low- and high-dose groups (2.8% vs 3.4%, respectively, P = .379). After propensity score matching, the high-dose group was still associated with a significant clinical benefit.


CONCLUSIONS
Our results show that a 600-mg loading dose followed by a 150-mg maintenance dose of clopidogrel within the first 15 days after PCI is independently associated with a decrease in the composite death-myocardial infarction-stent thrombosis at 2 months without increase in hemorrhagic complications.
Lemesle
Gilles
G
Hôpital cardiologique, Lille, France.
Delhaye
Cédric
C
Sudre
Arnaud
A
Broucqsault
Damien
D
Rosey
Guillaume
G
Bauters
Christophe
C
Lablanche
Jean-Marc
JM
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine