Global EP Summit: Device Infection

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Bruce Wilkoff, MD:

It is my pleasure to present the clinical and economic impact of CIED infections and cost-effectiveness of the TYRX envelope.

Bruce Wilkoff, MD:

I have the following relationships with industry, including those with Medtronic, Abbott, Philips and Convatec.

Bruce Wilkoff, MD:

The first issue to understand is why preventing infection is important. When we looked at the one-year mortality after patients presented to the Cleveland Clinic with a CIED infection, understanding that all of these patients were extracted and given antibiotics and treated to cure their infections, but their survival rate was poor with a 7 to 33 percent risk of dying within the first year. Thus, the only way to prevent mortality from infection would be to prevent the infection itself.

Bruce Wilkoff, MD:

This data was corroborated by a look at the National Cardiovascular Data Registry where in over 200,000 patients there was a 1.7 percent infection rate, and at six months, the patients had an almost doubling of the mortality rate from 6.5 percent to 12 percent.

Bruce Wilkoff, MD:

It was with this in mind that we performed the WRAP-IT clinical trial, which was an analysis of the antibacterial envelope to prevent infections in cardiac implantable devices. This was presented at the American College of Cardiology and published in the New England Journal of Medicine in March of 2019.

The primary endpoint for this study was to evaluate the safety and effectiveness of the TYRX absorbable antibacterial envelope in reducing CIED infections. The primary endpoint was at 12 months, comparing the mortality rate and infection rates and outcomes at 12 months of those patients required TYRX envelopes versus those who were randomized to control. It was an intention to treat analysis and patients were stratified between low power or pacemaker and high power or ICD devices.

Bruce Wilkoff, MD:

The primary endpoint was a reduction in major CIED infections at 12 months and a 40 percent reduction was identified with a reduction from 1.2 percent to 0.7 percent in those patients who received the antibacterial envelope. In these over 3,000 patients in both lens if we looked at the pocket infections, rather than total nature infections still at 12 months, we see that there was a 61 percent reduction in major CIED pocket infections with those patients with a TYRX envelope through 12 months.

Bruce Wilkoff, MD:

In addition to looking at the rate of infection and the efficacy of the envelope, we wanted to understand the impact of the cardiac implantable electronic device infections, and this was published in Circulation: AE earlier this year. Not surprisingly, there was an impact on mortality. There was also an improvement in mortality risk-adjusted with a hazard ratio of 3.41 when using the envelope. However, if we look at the rate of infection, we see something similar to what we saw in the non-randomized prior data. If we look from the time of randomization and look over the first 36 months, those patients without major infections had an 18 percent mortality rate and this increased to 25 percent in those patients who had a major infection. If instead of going from the time of randomization, we go from the time of infection and just look at the infection rate in those patients who received infections or developed infections, we see that at 12 months there was a 16 percent mortality rate and a 23 percent mortality rate at 24 months. This includes the 70 patients and 67 patients worldwide and 43 major infections in the US out of 41 patients in terms of all-cause mortality.

Bruce Wilkoff, MD:

Not surprisingly, the infections also affected quality of life. This impact occurred early at the time of infection diagnosis and persisted at one month and at three months and, in fact, it took six months before the quality of life, as measured by the EQ-5D utility, return to baseline.

Bruce Wilkoff, MD:

Also, without surprise, there was some disruption in the application of the CIED therapy. Necessarily, the CIEDs were removed in 59 of the 70 infections. In 11 patients, it was not possible to remove the device, so the CIED therapy continued, but with an impact on the therapy for the infection.

Bruce Wilkoff, MD:

Those patients who had their CIEDs removed were replaced during the same hospitalization in 29, and in 11 were replaced in a separate hospitalization, and in 14 went through the end of the study without having their device reimplanted, either because they could not or because it was no longer felt to be necessary, and you see these patients in yellow or orange on the slide. So there was disruption in these 25 patients out of the 70 for a significant length of time. In addition, there were the five patients who died prior to the replacement or infection resolution.

Bruce Wilkoff, MD:

In addition to the clinical cost, there is the financial cost and these costs are distributed between the hospital and the payer. The mean hospital cost was 55,000 dollars per infection with a mean hospital margin of a minus 30,828 dollars if the patient had Medicare Fee-For-Service and a minus 6,000 dollars for those patients with Medicare Advantage. Now, for the payer, Medicare in this case, the cost was 26,867 dollars for those with Medicare Fee-For-Service and 57,978 dollars for those patients who had Medicare Advantage. So, there was significant cost to the hospital and to the payer. In addition to the cost to the hospital and to the payer, there is cost that goes directly to the patient. For the patients who had Medicare Fee-For-Service, there was a median of 1,374 dollars, and for those patients with Medicare Advantage, the cost to the patient was 1,435 dollars.

Bruce Wilkoff, MD:

Once we had determined the clinical cost and the financial cost of device infections, we needed to study the cost-effectiveness of that investment. This was accepted for publication in Circulation: Arrhythmia and Electrophysiology in August of 2020. What we did is to model with a decision tree analysis with cost and outcomes over a lifelong time horizon. We took the WRAP-IT study patients and we use the United States Integrated Payer Provider Network. We took in the information from the WRAP-IT study and from other literature, which allowed us to have not just the infection rates and the envelope's effectiveness, but the life expectancy and the long-term costs associated with device replacement follow-up and healthcare utilization.

Bruce Wilkoff, MD:

Importantly, we used the willingness to pay threshold of 150,000 dollars per quality adjusted life year, which aligns with the American College of Cardiology and American Heart Association Practice Guidelines and contemporary analysis of this sort. This is a look at the decision tree analysis. As you can see, each branch is mutually exclusive. Either patients had an infection or did not have an infection, and they either survived or did not survive, and then they either survived or didn't survive with extraction or partial extraction, et cetera. Now, this decision tree time horizon is 12 months, but the model was extended to a lifetime perspective by assigning lumped cost-benefit estimates at endpoints A through H at each of these nodes on this decision tree.

Bruce Wilkoff, MD:

When we look at standard of care alone versus standard of care plus the antibacterial envelope, we see the cost through 12 months and the costs after 12 months and the total lifetime cost that's modeled here. The cost difference in US dollars was 671 dollars, and you'll see the life years saved changed from 7.597 to 7.603 with a life year's difference of 0.006. This gives us an ICER, or an incremental cost-effectiveness ratio, of 106,675 overall within the WRAP-IT study.

Bruce Wilkoff, MD:

Now, depending on the analysis, we needed to also look at sensitivity to variations in various parts of the model, and we found that 78 percent of the simulations looking at different life expectancies, infection cost, discount rates, infection disutilities, lifetime costs and extraction probability, all hovered around a hundred thousand, and in 78 percent of the simulations, they remained below 150,000 dollars.

Bruce Wilkoff, MD:

In the final analysis, the cost-effectiveness of the antibacterial envelope depended strongly and was influenced strongly by the standard of care infection rates. In this graph, we place the subgroups versus the standard of care infection rates versus the incremental cost-effectiveness ratio and the level of value in the four columns. You can see that patients with prior CIED infections, actually it was cost-saving to use the envelope, while it was of high value, less than 30,000 dollars or so, in those patients with pacemaker revisions and upgrades or defibrillators with two or more prior procedures or those people with a history of being immunocompromised.

Bruce Wilkoff, MD:

Not quite as good, but still of very strong value, less than 150,000 ICERs, we see those patients with renal dysfunction, defibrillators revisions and upgrades, pacemakers with two or more procedures and defibrillators with one prior procedure. It is only in those patients with pacemakers with just one prior procedure, so their initial device change, and in the CRTDs, the de novo implants, where it appeared to be less economically attractive. So we can see in many of the subgroups we had a very strong cost-effectiveness in this analysis.

Bruce Wilkoff, MD:

So in conclusion, the antibiotic envelope is cost-effective according to this contemporary comprehensive economic analysis, is based on lifetime costs and outcomes in the US healthcare system and is for the WRAP-IT study population. This analysis aligns with what is practice guidelines based on cost and value by the American College of Cardiology and the AHA. And the end result, this study provides strong evidence that the antibiotic envelope provides value for the US healthcare system in the prevention of CIED infections in this population.

Bruce Wilkoff, MD:

Overall, looking at the clinical and economic conclusions, CIED infections have a substantial impact on survival, quality of life, interruption of CIED therapy and the finances of the patient, hospital and society. Reducing CIED infections with the antibiotic envelope is not only cost-effective, but dependent on infection incidents and should be a primary focus of our care of these patients. Thank you.

Announcer:

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