Efficacy of drug eluting envelopes in reducing infections among pacemaker patients: the REINFORCE real-world data project

Abstract Introduction Infections associated with cardiac implantable electrical devices (CIEDs) are major complications that lead to prolonged hospitalizations, repeat surgeries, and higher healthcare costs. While previous studies, such as WRAP-IT, have demonstrated the efficacy of the absorbable antibiotic-eluting envelope, most data concern patients with implantable defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-D). Limited data are available on pacemaker (PM) or cardiac resynchronization therapy pacemaker (CRT-P) recipients. Purpose This analysis evaluates the effectiveness of the TYRX envelope in preventing systemic and pocket infections in a real-world population of PM and CRT patients. Methods This multicenter retrospective cohort included 896 patients who underwent PM or CRT implantation or system-related surgery at nine Italian centers between August 2020 and April 2024. The study population was divided into two groups: the Envelope group (n=350) and the control group (n=546). Clinical characteristics, procedural details, and infection-related outcomes were analyzed. Kaplan-Meier survival analysis and univariate/multivariate Cox analysis were used to assess the incidence and predictors of systemic and pocket infections. Results Patients in the Envelope group had more comorbidities, including heart failure, diabetes, and a higher CHA2DS2-VASc score, compared to the control group. During a mean follow-up of 2.2 ± 2.1 years, infections were significantly less frequent in the Envelope group (0.3%) than in the control group (1.8%) (p=0.05). The incidence rate of systemic or pocket infections was 0.01 per 100 patient-months in the Envelope group versus 0.09 in the control group, resulting in an 89% risk reduction (IRR: 0.11, 95% CI: 0.05-0.23, p<0.001). Kaplan-Meier survival analysis demonstrated a significant protective effect of the TYRX envelope, with a cumulative infection incidence of 0.4% in the Envelope group versus 2.5% in the control group at four years (HR: 7.36, p=0.03). The protective effect of drug eluting envelope persisted over time, with no significant increase in infection rates in the Envelope group after the first 12 months. Conclusion This analysis demonstrates that the antibacterial envelope significantly reduces the risk of systemic and pocket infections in patients with pacemakers and CRT-P devices. Despite the higher comorbidity burden in the Envelope group, the envelope's protective effect remained significant over four years. These findings support the routine use of drug eluting envelopes in patients undergoing pacemaker or CRT implantation to minimize the risk of infections.