Antibacterial Envelope to Prevent Cardiac Implantable Device Infection.

BACKGROUND: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial.

BACKGROUND: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. METHODS: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. RESULTS: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. CONCLUSIONS: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.