NEW ORLEANS — The first randomized trial to evaluate the TYRX absorbable antibacterial envelope (Medtronic) shows that it significantly reduces the risk for major cardiac implantable electronic device (CIED) infections when added to standard infection-prevention strategies.
Patients whose device was enclosed in the envelope had a 40% relative risk reduction in the primary outcome of major infection resulting in device extraction or revision, long-term antibiotic therapy with infection recurrence, or death within 1 year, compared with standard care alone (hazard ratio [HR], 0.60; 95% CI, 0.36 - 0.98).
The absolute risk reduction was 0.5% (from 1.2% to 0.7%), according to results from the WRAP-IT study, which were reported here at the ACC 2019 Scientific Session (ACC.19) and simultaneously published online March 17 in the New England Journal of Medicine.
"This study provides comprehensive data on CIED infection and strong evidence for use of the TYRX envelope for infection prevention in this patient population," concluded lead author Khaldoun Tarakji, MD, MPH, from the Cleveland Clinic.
The multifilament mesh envelope has long been available in the United States and Europe and is designed to release minocycline and rifampin for 7 days and dissolve after 9 weeks. A nonabsorbable version that is no longer available in the United States showed an 80% reduction in 1-year CIED infections in a combined registry comparison with historic control subjects.
Although the modest absolute risk reduction in the primary end point could be a target of criticism, the overall low infection rate is "something to celebrate" and TYRX reduced it even further, Tarakji told theheart.org | Medscape Cardiology.
"You cannot have full respect for that 1.2% if you are not familiar with what an infection means for somebody who had a device implanted as a primary prevention and now they have to deal with all these risks of infection, including the extraction, the long hospitalization, and the finances of this as well," he said.
Further, even when a device is removed and the infection clear, he noted that data from multiple large centers consistently show "30-day mortality of 4% to 5% and 1-year mortality that could be anywhere from 8% to 15%, and sometimes even higher."
Panelist and electrophysiologist Kristen Patton, MD, University of Washington, Seattle, however, questioned why the trial excluded patients at the highest risk for infection — those taking chronic oral immunosuppressive agents or at least 20 mg of prednisone, those requiring dialysis, or those with a history of device infection within 12 months — and whether the envelope should be used in all-comers given a number-needed-to-treat (NNT) of about 200.
Tarakji replied that TRYX is designed to prevent pocket infection and that patients on dialysis represent an entirely different risk group. Exclusion of a recent infection was mainly to avoid confusion over whether this was a new infection or edema from a previous one.
"We put a lot of thought into this and I hope we made the right decision, but we truly wanted this to reflect the common patient coming for simple device change and not to include the exceptionally high-risk patient population to be able to apply this to the general public," he said.
Tarakji said the latest iteration has been proven to be effective and safe and should be used in all patients meeting the study criteria.
Operators at 181 centers in 25 countries randomly assigned 6983 patients undergoing CIED generator replacement, system upgrade, or revision or initial CRT-D implantation to standard preprocedure intravenous antibiotics and sterile technique with or without the envelope.
The average patient age was 70 years, one-quarter of the participants were female, and about 16% had renal dysfunction. The envelope and standard-care groups had similar use of periprocedural antibiotics (98.6% vs 98.7%), postprocedural antibiotics (28.6% vs 30.6%), and pocket wash (73.6% vs 75.5); however, immunosuppressive use was not balanced between the two groups (1.4% vs 2.4%).
TYRX was successfully impIanted in 99.7% of patients. The add-on device was associated with a 61% reduction in major pocket infections within a year (14 vs 36 events; HR, 0.39; 95% CI, 0.21 - 0.72) but higher rates of bacteremia or endocarditis (11 vs 6 events; HR, 1.57; 95% CI, 0.61 - 4.05).
Differentiation between pocket and endovascular infections can be very vague and the number of events way too small to draw any conclusions, Tarakji said when asked by theheart.org | Medscape Cardiology about the finding.
TYRX did not increase the risk for complications compared with standard care alone in the year after the procedure (6.0% vs 6.9%) or major CIED infections through the 36-month follow-up period (1.3% vs 1.9%).
"It looks like you're going to take some of my business away with this device," quipped panelist David Mushatt, MD, MPH, chief of infectious diseases, Tulane University, New Orleans. "These results are truly impressive when you consider that many of these infections are in fact secondary to seeding of bacteremia from a remote site, in which case one would not expect the antibiotic-permeated mesh to have an impact."
He reminded the audience that 30% of the patients received postprocedural antibiotics — "a practice that we discourage. I hope that this study gives them reason not to."
Mushatt observed that immunosuppressive use was twice as high in the control group but said the numbers were small and unlikely to have made a difference in the results.
During a press briefing, discussant Dhanunjaya Lakireddy, MD, medical director, Kansas City Heart Rhythm Institute, Overland Park, said it is important to bring device infections down to zero because they can be devastating to the patient, but noted that with an NNT of 200, it would cost approximately $200,000 to prevent one device infection.
"Leaving an antibiotic inside the pocket seems to be an attractive theory, but do we really need a pouch or can we get away with something much cheaper?" he said. "Again, wonderful study. thIs is a game changer for all of us who are involved in device patients and device infections."
The study was funded by Medtronic. Tarakji reports nonfinancial support from Cleveland Clinic C5 during the conduct of the study and personal fees from Medtronic and AliveCor.
N Engl J Med. Published online March 17, 2019. Full text
American College of Cardiology (ACC) 2019 Scientific Session. Presented March 17, 2019.
Medscape Medical News © 2019
Cite this: WRAP-IT: Antibacterial Pouch Cuts Device Infections - Medscape - Mar 18, 2019.