Increased risk of bleeding in patients on clopidogrel therapy after drug-eluting stents implantation: insights from the HMO Research Network-Stent Registry (HMORN-stent).
BACKGROUND
Studies suggest that extended clopidogrel use after drug-eluting stent (DES) implantation may decrease the risk of myocardial infarction (MI) and death. Little is known about the competing risk of bleeding from clopidogrel in "real world" clinical practice.


RESULTS
We studied 7689 patients undergoing drug-eluting stent implantation enrolled in the HMO Research Network-Stent Registry between 2004 and 2007. Patients were analyzed in 6-month intervals for the occurrence of major bleeding, MI, and death. Clopidogrel use was determined by pharmacy dispensing data. Regression models assessed the association between clopidogrel use and outcomes. Overall, 3603 patients (49.1%) received clopidogrel for >6 months. During a mean follow-up of 418 days (SD, +/-168 days), 217 (2.9%) patients died, 279 (3.7%) had a MI, and 271 (3.6%) had major bleeding. After adjustment, patients on clopidogrel therapy were associated with increased major bleeding in all time intervals (0 to 6 months: relative risk (RR)=2.70, 95% CI=1.41 to 5.19; 7 to 12 months: RR=1.71, 95% CI=1.05 to 2.79; 13 to 18 months: RR=2.34, 95% CI=1.26 to 4.34), compared with patients off clopidogrel. Clopidogrel use was also associated with decreased risk of MI for all time intervals (0 to 6 months: RR=0.52, 95% CI=0.36 to 0.77; 7 to 12 months: RR=0.46, 95% CI=0.30 to 0.70; 13 to 18 months: RR=0.53, 95% CI=0.29 to 0.99) and decreased death in the 7 to 12 month interval (RR=0.50, 95% CI=0.30 to 0.83).


CONCLUSIONS
Clopidogrel use was associated with increased major bleeding and decreased MI persisting to 18 months. Bleeding risks on clopidogrel therapy deserve consideration in the ongoing debate regarding optimal clopidogrel duration after PCI.
Tsai
Thomas T
TT
Denver VA Medical Center, Denver, CO 80220, USA. thomas.tsai@coloradooutcomes.org
Ho
P Michael
PM
Xu
Stanley
S
Powers
J David
JD
Carroll
Nikki M
NM
Shetterly
Susan M
SM
Maddox
Thomas M
TM
Rumsfeld
John S
JS
Margolis
Karen
K
Go
Alan S
AS
Magid
David J
DJ
D000368:Aged; D000077144:Clopidogrel; D015897:Comorbidity; D054855:Drug-Eluting Stents / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006279:Health Maintenance Organizations; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D019106:Postoperative Hemorrhage / Q000453:epidemiology / Q000209:etiology*; D019919:Prosthesis Implantation; D012042:Registries; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000077144:Clopidogrel; D013988:Ticlopidine