Surgical site infections and blood infections after coronary artery bypass surgery are major causes of morbidity and mortality; therefore, there is great interest in identifying modifiable risk factors that may help identify patients at increased risk for those complications. There is evidence that platelets play an important role in innate and adaptive immunity responses and it is known that some of the most used drugs in patients undergoing coronary artery bypass surgery, clopidogrel and statins, modify platelet reactivity. The objective of this dissertation was to investigate the association of clopidogrel, in the context of dual antiplatelet therapy, and statins with postoperative infections in a cohort of patients undergoing coronary artery by pass surgery from Johns Hopkins Hospital.

First, we conducted a review of the biological plausibility of the role of platelets in the defense against microorganism, we described the mechanism of action of clopidogrel and the pleiotropic effects of statins and, finally, we reviewed the experimental and epidemiological evidence on clopidogrel and statins and risk of infectious complications. The literature review on clopidogrel showed that preoperative use of clopidogrel increases the risk of postoperative bleeding and blood transfusion but we didn't find evidence of increased risk of postoperative infections. The literature review on statins showed that statins were associated with a decreased risk of pneumonia, sepsis, all-cause and infection-related mortality and postoperative infections after cardiac surgery.

Second, we conducted a retrospective cohort study of patients undergoing coronary artery bypass surgery at Johns Hopkins Hospital from January 1, 2000 through June 2003 who have taken aspirin preoperatively to evaluate the association between preoperative use of clopidogrel, in the context of dual antiplatelet therapy, and incidence of postoperative infections. The cumulative incidence of infection at 30 days was 23.1% in patients on dual antiplatelet therapy with clopidogrel and 16.3% in patients on aspirin alone (crude hazard ratio: 1.51; 95%CI: 1.09–2.08). After propensity score adjustment, the hazard ratio for postoperative infection comparing patients on dual antiplatelet therapy with clopidogrel to those only on aspirin was 1.43 (95% CI: 1.01–2.01). The association was consistent in most subgroups examined. Preoperative use of dual antiplatelet was also associated with increased postoperative bleeding (adjusted average blood loss: 150.4 ml; 95% CI: 90.59–210.24 ml) and with an increased risk of postoperative blood transfusion requirements (adjusted OR: 1.51; 95% CI: 1.03–2.22).

Third, we conducted a retrospective cohort study of patients undergoing coronary artery bypass surgery at Johns Hopkins Hospital from January 1, 2000 through June 2003 to evaluate the association between preoperative use of statins and incidence of postoperative infections. The cumulative incidence of infection at 30-days was 17.1% in patients using statins prior to surgery and 16.3% in patients not using statins (crude hazard ratio: 1.04; 95% CI: 0.84–1.28). The adjusted hazard ratio for postoperative infectious complications comparing patients taking statins to those not taking statins was 1.03 (95% CI: 0.83–1.28). Also, preoperative use of statins was not associated with increased risk of blood transfusion (adjusted odds ratio: 1.04; 95% CI: 0.84–1.28) or post-operative bleeding (adjusted average difference: -14.5 ml; 95% CI: -49.0 to 20.0 ml).

In conclusion, in the cohort of patients undergoing coronary artery bypass surgery at Johns Hopkins Hospital from January 1, 2000 through June 30, 2003 preoperative use of clopidogrel, in the context of dual antiplatelet therapy, was associated with an increased risk of postoperative infectious complications, postoperative bleeding and blood transfusion requirements; preoperative use of statins was not associated with an increased risk of postoperative infectious complications, postoperative bleeding and blood transfusion requirements. Although the implications of preoperative use of clopidogrel on postoperative infections are important, we claim caution to modify the actual clinical practice of discontinuing/continuing regular use of clopidogrel before a coronary artery bypass graft surgery procedure because first, our results should be confirmed by other cohort studies and particularly by clinical trials and second, there is some evidence in the literature of higher risk of cardiovascular events and death in the first months after stopping treatment with clopidogrel.