Impact of Cardiac Implantable Electronic Device Infection: A Clinical and Economic Analysis of the WRAP-IT Trial

Abstract

Background: Current understanding of the impact of cardiac implantable electronic device (CIED) infection is based on retrospective analyses from medical records or administrative claims data. The WRAP-IT (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial) offers an opportunity to evaluate the clinical and economic impacts of CIED infection from the hospital, payer, and patient perspectives in the US healthcare system.

Methods: This was a prespecified, as-treated analysis evaluating outcomes related to major CIED infections: mortality, quality of life, disruption of CIED therapy, healthcare utilization, and costs. Payer costs were assigned using medicare fee for service national payments, while medicare advantage, hospital, and patient costs were derived from similar hospital admissions in administrative datasets.

Results: Major CIED infection was associated with increased all-cause mortality (12-month risk-adjusted hazard ratio, 3.41 [95% CI, 1.81-6.41]; P<0.001), an effect that sustained beyond 12 months (hazard ratio through all follow-up, 2.30 [95% CI, 1.29-4.07]; P=0.004). Quality of life was reduced (P=0.004) and did not normalize for 6 months. Disruptions in CIED therapy were experienced in 36% of infections for a median duration of 184 days. Mean costs were $55 547±$45 802 for the hospital, $26 867±$14 893, for medicare fee for service and $57 978±$29 431 for Medicare Advantage (mean hospital margin of -$30 828±$39 757 for medicare fee for service and -$6055±$45 033 for medicare advantage). Mean out-of-pocket costs for patients were $2156±$1999 for medicare fee for service, and $1658±$1250 for medicare advantage.

Conclusions: This large, prospective analysis corroborates and extends understanding of the impact of CIED infections as seen in real-world datasets. CIED infections severely impact mortality, quality of life, healthcare utilization, and cost in the US healthcare system. Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02277990.

Keywords: administrative claims, healthcare; antibiotic; economics; infections; quality of life.

Figure 1.

Kaplan-Meier all-cause mortality curves. A, Patients with (cohort with major infections) and without infections (cohort with no major infections). Hazard ratios and P values are calculated using Cox proportional regression modeling. As compared with the no infection group, infections were associated with an increased risk of death. The effect on mortality was sustained beyond 12 mo. B, Kaplan-Meier (KM) curve and 95% CI for patients with major infection from infection onset. Of the patients in the cohort with major infections, the KM estimates of mortality after major infection onset were 16% at 12 mo and 23% at 24 mo.

Figure 2.

Quality of life. Impact of infections on quality of life. Data were analyzed using linear mixed-effects modeling. EuroQOL-5D utilities were significantly reduced at time of infection diagnosis vs baseline and did not normalize until 6 mo post-diagnosis. Dots represent the mean and the whiskers represent the 95% CI.

Figure 3.

Cardiac implantable electronic device (CIED) therapy disruption. Time spent without previously indicated CIED therapy. Widths of the paths are proportional to the number of patients in the Sankey Diagram indicating treatment pathway for infections with (blue) and without (orange) CIED therapy disruption. Approximately 36% of infections involved disruption of CIED therapy.

Figure 4.

Payer and hospital costs and margins. A, Total payer costs per infection in the US Cohort with Major Infections for Medicare fee for service (FFS) and Medicare Advantage. B, Total hospital costs and margins per infection in the US Cohort with major infections based on Medicare FFS and Medicare Advantage payments. Box-and-whisker plots represent distribution of data as follows: solid line=median; dashed line=mean; box=interquartile range; whiskers=minimum and maximum within 1.5× interquartile range; dots=outliers (outside of 1.5× interquartile range). All currency reflects 2017 US dollars.