**3.5 Concerns about aspirin use in hemodialysis patients**

The abuse of non steroidal inflammatory drugs is a well described risk factor for upper gastrointestinal bleeding. The concern has been raised that the use of aspirin in dialysis patients could be harmful by causing bleeding (Chan et al., 2003 and 2008). As noted in a recent metanalysis the available data is conflicting for a variety of reasons such as selection bias, insufficient length of follow up and concomitant treatment with proton pump inhibitors (Hiremath et al., 2009). In the study of Chan et al a trend towards a higher incidence of bleeding was observed which did not reach statistical significance as both the initial study as well as the subsequent post hoc analysis was underpowered to either

death from septicemia due to vascular access in USRDS data. These results provide a confirmation of a clinical anti-staphylococcal effect of aspirin in hemodialysis patient that is

Age (y) 1.0 (1.0-1.0) 0.99 Time on dialysis (d) 1.0 (1.0-1.001) 0.88 Catheter no. 0.95 (0.83-1.09) 0.45 Female sex 1.19 (0.76-1.86) 0.45 Tobacco use 0.78 (0.49-1.24) 0.30 Diabetes mellitus 1.65 (1.02-2.67) 0.04\* Hypertension 1.36 (0.74-2.51) 0.33 COPD 0.49 (0.24-0.97) 0.04\* Coronary artery disease 0.80 (0.48-1.34) 0.40 Peripheral vascular disease 1.01 (0.62-1.65) 0.97 Stroke 1.11 (0.63-1.96) 0.72 Arthritis 1.22 (0.78-1.92) 0.39 Cancer 1.04 (0.59-1.83) 0.89 Previous transplant 1.19 (0.55-2.55) 0.66 Clopidogrel 1.06 (0.40-2.83) 0.91 Warfarin 1.79 (1.03-3.10) 0.04\* Statin 1.08 (0.63-1.85) 0.79 B-Blocker 1.13 (0.70-1.83) 0.62 ACE inhibitor/ARB 0.79 (0.50-1.25) 0.31 Calcium channel blocker 0.73 (0.46-1.15) 0.17 Aspirin 0.46 (0.28-0.76) 0.002\* Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker.

Table 4. Risk of First *S aureus* Bacteremia Episode in 872 Dialysis Patients with a Tunneled

The abuse of non steroidal inflammatory drugs is a well described risk factor for upper gastrointestinal bleeding. The concern has been raised that the use of aspirin in dialysis patients could be harmful by causing bleeding (Chan et al., 2003 and 2008). As noted in a recent metanalysis the available data is conflicting for a variety of reasons such as selection bias, insufficient length of follow up and concomitant treatment with proton pump inhibitors (Hiremath et al., 2009). In the study of Chan et al a trend towards a higher incidence of bleeding was observed which did not reach statistical significance as both the initial study as well as the subsequent post hoc analysis was underpowered to either

Reprinted from Sedlacek et al.: "Aspirin Treatment Is Associated With a Significantly Decreased Risk of Staphylococcus aureus bacteremia in Hemodialysis Patients With Tunneled Catheters", Am J Kidney Dis Vol49, pp401-408 with permission from Elsevier

**Relative Risk (95% CI)** *P*

independent from the data pool used in our first study.

\*Statistical significance in Cox proportional hazard model.

**3.5 Concerns about aspirin use in hemodialysis patients** 

Catheter by using Cox Proportional Hazard Analysis

Fig. 1. Cumulative plot of tunneled catheter failure associated with *S aureus* bacteremia. The failure plot was obtained using the Kaplan-Meier method. Tics represent censoring of catheter removal unrelated to *S aureus* bacteremia. Log-rank test was used to calculate *P*. Reprinted from Sedlacek et al.: "Aspirin Treatment Is Associated With a Significantly Decreased Risk of Staphylococcus aureus bacteremia in Hemodialysis Patients With Tunneled Catheters", Am J Kidney Dis Vol49, pp401-408 with permission from Elsevier

support or refute this hypothesis. In our own study no increased risk of bleeding was observed (unpublished data, Sedlacek et al., 2008). A study on aspirin use in 28320 patients from the Dialysis Outcomes and Practice Patterns Study I and II found neither a decreased cardiovascular risk nor an increase in the gastrointestinal bleeding with the use of aspirin (Ethier J et al., 2007). (Of note, no data on infectious complications was included in this manuscript which why it was not discussed in the above sections.)

While there is no unequivocal proof that aspirin increases the risk of upper gastrointestinal bleeding in dialysis patients, it must not be forgotten that upper gastrointestinal bleeding is a well documented part of the uremic syndrome and that anticoagulation is routinely used during the hemodialysis procedure. It would thus seem reasonable to adopt a similar approach to high risk dialysis patients as has been recommended in high risk cardiac patients who would benefit from aspirin. Patients can be screened and treated for *H.pylorii* and proton pump inhibitors may be considered. Lastly it has to be noted that upper gastrointestinal bleeding is more amenable to treatment and represents a lesser risk to a high risk dialysis patient than for example cardiac stent occlusion.
