Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy.
OBJECTIVE
To characterize the safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention (PCI), and to identify patient characteristics that increase the risk of hemorrhage.


METHODS
Retrospective, matched cohort study.


METHODS
Academic medical center and affiliated outpatient offices.


METHODS
The active group consisted of 97 patients who underwent PCI from January 1, 2000-September 30, 2005, and received warfarin, aspirin, and clopidogrel; the control group consisted of 97 patients who were individually matched to patients in the active group by procedure type, procedure year, age, and sex. Control patients received aspirin and clopidogrel.


RESULTS
Clinical data were collected from inpatient records, outpatient physician office records, and telephone surveys administered to patients or caregivers. The primary end point was major bleeding. The median duration of follow-up after index procedure was 182 days (range 0-191 days) in the active group and 182 days (range 0-213 days) in the control group. Fifty-seven (59%) of the 97 patients in the active group received warfarin for atrial fibrillation. There were 14 major bleeds in the active group (including 1 death) and 3 major bleeds in the control group during the study period. Mean international normalized ratio at the time of bleeding was 3.4. Hazard ratio for major bleeding was 5.0 in patients receiving warfarin therapy (95% confidence interval 1.4-17.8, p=0.012). Aspirin dose, age, sex, body mass index, history of hypertension, diabetes mellitus, intraprocedural glycoprotein IIb-IIIa or anticoagulant type, and postprocedural anticoagulant use did not have a significant effect on the risk of major bleeding.


CONCLUSIONS
Warfarin was an independent predictor of major bleeding after PCI in patients receiving dual antiplatelet therapy. Prospective data to further characterize the safety of concomitant warfarin and dual antiplatelet therapy after PCI are needed.
DeEugenio
Deborah
D
Department of Pharmacy Practice, College of Pharmacy, Temple University, Philadelphia, Pennsylvania, USA. ddeeugen@temple.edu
Kolman
Louis
L
DeCaro
Matthew
M
Andrel
Jocelyn
J
Chervoneva
Inna
I
Duong
Phu
P
Lam
Linh
L
McGowan
Christopher
C
Lee
Grace
G
DeCaro
Mark
M
Ruggiero
Nicholas
N
Singhal
Shalabh
S
Greenspon
Arnold
A
D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy; D000077144:Clopidogrel; D015331:Cohort Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin