In-hospital patients exposed to clopidogrel before coronary artery bypass graft surgery: a word of caution.
BACKGROUND
The aim of our study was to investigate the independent effect of preoperative exposure to aspirin, heparin, and clopidogrel on early clinical outcomes of in-hospital referral patients undergoing first time coronary artery bypass graft (CABG) surgery.


METHODS
Outcomes for in-hospital referrals for CABG between January 2001 and January 2002 were prospectively recorded. Exposure to aspirin, heparin, and clopidogrel during the 5 days before surgery was recorded, and their effect on outcome was explored using multiple regression methods. The effect of clopidogrel given within 48 hours before surgery versus stopped at least 48 hours before the operation was also investigated.


RESULTS
In-hospital referral patients represented 40% (473 of 1,185) of the total surgical population; 304 (64.7%) were prescribed aspirin, 116 (24.7%) heparin, 91 (19.4%) clopidogrel, and 133 (28.3%) had all anticoagulants stopped 5 days before surgery. In-hospital mortality was 2.3% (95% confidence interval [CI]: 1.1 to 4.1) and was highest among those exposed to clopidogrel (odds ratio 16.9, 95% CI: 2.10 to 136, p = 0.008). Seven of the 11 deaths occurred in patients given clopidogrel. Postoperative intraaortic balloon pump, arrhythmia, reintubation, and stroke were all significantly more common when clopidogrel was prescribed (relative risk estimates all greater than 1.5, p values all < or = 0.021). Blood loss was 37% higher in the patients given clopidogrel (95% CI: +3% to +82%, p = 0.033). Clopidogrel patients were more likely to need a reoperation for bleeding (p < 0.001) and require transfusions (p < or = 0.015). Intubation time and hospital stay were also longer (p = 0.021 and p = 0.019, respectively). Heparin was also associated with longer hospital stay (p < 0.001) and aspirin use with reduced stay (p = 0.041), but for all other outcomes, no association with aspirin or heparin use was found. Comparison of subgroups of clopidogrel patients suggested mortality was highest when clopidogrel was given in the 48 hours before surgery.


CONCLUSIONS
Our study suggests that among in-hospital referral patients, preoperative exposure to clopidogrel within 5 days before CABG may increase early mortality and morbidity, and that the mortality risk is greatest when the drug is given within 48 hours of surgery.
Ascione
Raimondo
R
Bristol Heart Institute, Bristol Royal Infirmary, Bristol, United Kingdom. r.ascione@bristol.ac.uk
Ghosh
Arup
A
Rogers
Chris A
CA
Cohen
Alan
A
Monk
Chris
C
Angelini
Gianni D
GD
D000368:Aged; D001241:Aspirin / Q000009:adverse effects; D016063:Blood Loss, Surgical; D000077144:Clopidogrel; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000401:mortality; D005260:Female; D006493:Heparin / Q000009:adverse effects; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012017:Referral and Consultation; D020521:Stroke / Q000209:etiology; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin