Trends in Targeted Temperature Management Before and After 2013, with José López, MD

An analysis of data from the National Inpatient Sample over 15 years details the impact of the 2013 publication of the TTM trial on use of targeted temperature management (TTM) in the US.

Presented at the American College of Cardiology 2024 (ACC.24) Annual Scientific Session, results of the analysis suggest use of TTM in out-of-hospital cardiac arrest survivors increased steadily from 2005 through 2013, but saw a decline each year after, which investigators worry may represent a misinterpretation of study findings.

An international, multicenter, randomized trial, the TTM trial, which was published in the New England Journal of Medicine, randomized 950 unconscious adults with out-of-hospital cardiac arrest of presumed cardiac cause in a 1:1 ratio to targeted temperature management at either 33°C or 36°C. The trial’s primary outcome of interest was all-cause mortality through the end of the trial, which had a mean follow-up of 256 days.

Results of the trial indicated all-cause mortality occurred among 50% of the 33°C group and 48% of the patients in the 36°C group (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P = .51). Secondary analyses in the trial concluded 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P = .78).

In the ACC.24 presentation, investigators sought to describe trends in TTM use and predictors in the US before and after the publication of the TTM trial. With this in mind, investigators designed their study as an analysis of data from the National Inpatient Sample. Using 2005 through 2020 as the period of interest, investigators identified 2,803,130 admissions, including 53,858 (1.92%) who received TTM.

Upon analysis, results indicated TTM use was lowest in 2005, when rates reached 0.45%, and peaked at 3.44% in 2013 (P <.001). However, a subsequent decline was observed following this point (Trend: -0.27%; P <.001). Analysis of predictors suggested Black and Hispanic patients were less likely to receive TTM than White patients (OR, 0.87 and 0.64; P <.001). Investigators also pointed out those receiving care at urban teaching and non-teaching hospitals (OR, 1.98 and 1.91; P <.001) had greater likelihood of receiving TTM.

For more on the study and trends in TTM use in the US, check out our interview with study investigator José López, MD, cardiology fellow at the University of Miami JFK Medical Center, from the conference floor at ACC.24.

HCPLive: Can you describe the impetus behind this analysis?

Lopez: So, I got the idea with the first author, Dr. Justin Mark. We came up with this idea because around the publication of the TTM trial, there was a lot of talk and controversy about whether TTM was useful or not. Many doctors, even at my hospital, were discussing how they didn't want to use TTM anymore because they believed it didn't work. However, as I was diving deeper into the topic and read through all the trials, I realized there might have been a misinterpretation of the data. That's when the idea hit me—let's see if we can correlate the utilization of TTM with the publication of these trials and examine it over a broad timeline. That's why we looked at TTM utilization from 2005 to 2020, and we found some really interesting findings.

HCPLive: What were the results and why are they important?

Lopez: We essentially utilized the National Inpatient Sample and examined patients with any type of cardiac arrest admitted to the hospital between 2005 and 2020. Our focus was on the utilization of TTM. We discovered that out of more than 2.8 million post-cardiac arrest patients during this period, only 1.92% received TTM, totaling about 53,850. This low utilization rate indicates that the therapy is underutilized, considering it is indicated for more patients.

The second significant finding was that TTM utilization was increasing until 2013, after which it sharply declined. This decline can be correlated with the publication of different trials. For instance, the HACAT and Bernard trials published in 2000 demonstrated that TTM, cooling to target temperatures of 33 to 36 degrees Celsius, was superior to maintaining a temperature of 37 degrees Celsius in improving neurological outcomes in patients with shockable rhythm.

However, when the TTM trial was published in 2013, the same year, utilization started to decline. This trial showed no difference in mortality or neurological deficits. Yet, I believe a few crucial aspects of the study were overlooked. First, the TTM trial lacked a comparison arm, comparing only 33 degrees to 36 degrees without comparing to normothermia. Second, patients in that trial had a longer time to resuscitation, which suggests a higher degree of neurological injury. These trials are important, but I believe they may have been misinterpreted, leading to decreased utilization of this therapy, despite its significant role in select patient populations.

References:

1. Mark J, Lopez J, Colombo R, et al. TEMPORAL TRENDS AND PREDICTORS OF TARGETED TEMPERATURE MANAGEMENT IMPLEMENTATION FOR CARDIAC ARREST SURVIVORS. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. doi:10.1056/NEJMoa1310519