Use of recombinant tissue plasminogen activator (rt-PA) instead of heparin once weekly as a locking solution for central venous catheters in hemodialysis (HD) patients significantly decreases the risk of catheter malfunction and bacteremia compared with using heparin three times a week, according to Canadian researchers.

Investigators led by Brenda R. Hemmelgarn, MD, PhD, of the University of Calgary and Foothills Medical Centre in Calgary, Alberta, cited studies showing that approximately 50% of HD catheters fail within one year and as much as two thirds of failures are related to thrombosis.

The study included 225 patients undergoing long-term thrice-weekly HD in whom a central venous catheter had been newly inserted. Researchers randomly assigned 115 patients to receive a catheter-locking regimen of heparin (5,000 U/mL) three times per week and 110 patients to receive rt-PA (1 mg in each lumen) once weekly. The medication was substituted for heparin at the midweek session and heparin was used in the other two sessions. The treatment regimen was six months. The median duration of follow-up was 89 days in the heparin-only group and 115.5 days in the rt-PA group.

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Catheter malfunction occurred in 40 (34.8%) of the heparin-only patients compared with only 22 (20%) of the rt-PA recipients, Dr. Hemmelgarn’s group reported in The New England Journal of Medicine (2011;364:303-312). Compared with the rt-PA group, heparin-only patients had a nearly twofold increased risk of catheter malfunction.

In addition, catheter-related bacteremia occurred in 15 subjects (13%) in the heparin-only group versus only five rt-PA recipients (4.5%), a significant difference between the groups that corresponded to 1.37 and 0.40 episodes per 1,000 patient-days in the heparin-only and rt-PA groups, respectively. The heparin-only group had a threefold greater risk of bacteremia from any cause compared with the rt-PA group. The two groups were similar with respect to the risk of adverse events, including bleeding.

“These results are important,” said Dr. Hemmelgarn, an associate professor in the departments of medicine and community health services, “as they show that use of rt-PA can reduce the rates of these common complications experienced by hemodialysis patients with central venous catheters, to ultimately improve their long term outcomes.”

Hoffmann-La Roche, a maker of rt-PA, funded the study but had no role in the design or conduct or any other aspect of the study, the researchers noted.

In an accompanying editorial (pp. 371-373), Wolfgang C. Winkelmayer, MD, ScD, of the Division of Nephrology at Stanford University School of Medicine in Palo Alto, Calif., said the study by Dr. Hemmelgarn’s group as well as some other recent findings “allow tempered optimism that we are now making some progress in providing quality evidence to improve the care of the vascular access in patients with chronic kidney disease who currently require dialysis.”

However, he added: “But there is still a long and treacherous journey ahead until the day we might be able to say that vascular access used to be the Achilles’ heel of hemodialysis.”