Increased mortality after coronary stenting in patients treated with clopidogrel without loading dose. Evidence from a meta-analysis.
OBJECTIVE
Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its hematologic safety, but its efficacy in comparison to ticlopidine is debated. We thus systematically reviewed randomized trials comparing clopidogrel vs ticlopidine after coronary stenting.


METHODS
Medline (1/1986-10/2003), BioMed Central, Central, Current Contents, LILACS and mRCT were searched. Fixed-effect relative risks (RR [95% CI]) were computed, and the primary end-point was death. Heterogeneity tests and subgroup analyses were performed according to loading vs non-loading clopidogrel scheme.


RESULTS
Five trials were retrieved (2 962 patients, average follow-up 7.4 months). In 3 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (p for heterogeneity=0.12) showed a non-significant trend toward increased mortality in patients treated with clopidogrel (38/1 649 [2.3%]) vs ticlopidine (22/1 313 [1.7%], RR=1.64 [0.94-2.86], p=0.080). After stratification, clopidogrel with loading was associated with non-significantly lower mortality rates than ticlopidine (9/959 [0.9%] vs 13/798 [1.6%], RR=0.68 [0.29-1.63], p=0.39). Instead, clopidogrel without any loading yielded a highly significantly 3-fold increased risk of death than ticlopidine (29/690 [4.2%] vs 9/515 [1.7%], RR=2.9 [1.45-6.1], p=0.0029). Similar results were obtained for the rate of death or non-fatal myocardial infarction.


CONCLUSIONS
This meta-analysis suggests that clopidogrel treatment including a loading regimen is equivalent or may even be superior to ticlopidine after coronary stenting. However, current evidence shows conversely that clopidogrel therapy in the absence of a loading dose is associated with a significantly higher risk of death or myocardial infarction.
Biondi-Zoccai
G G L
GG
Institute of Cardiology, Caholic University, Rome, Italy. gbiondizoccai@tiscali.it
Agostoni
P
P
Testa
L
L
Abbate
A
A
Parisi
Q
Q
Burzotta
F
F
Trani
C
C
Mongiardo
R
R
Vassanelli
C
C
Biasucci
L M
LM
D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality* / Q000601:surgery; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine