Background: Pulmonary embolism (PE) is still a leading cause of morbidity and mortality in the

United States (US) despite recent advances in its treatment. Systemic thrombolysis (ST),

standard catheter-directed thrombolysis (SCDT), and ultrasound-assisted thrombolysis

(USAT) are all treatment approaches for PE utilized in the US today. Unfortunately, there

is limited data comparing these treatment approaches to PE. This study aimed to

investigate trends, outcomes, and predictors of mortality of ST vs. SCDT vs. USAT from

a nationally representative sample.

Methods: In‐hospital mortality and cost were collected from the National Inpatient Sample (NIS)

database for patients that underwent treatment for PE from 2011 to 2022. Secondary

outcomes included length of stay, disposition, and perioperative complications. We used

inverse probability of treatment weighting (IPTW) to adjust for differences in patient

demographics, comorbidities, and hospital baseline characteristics, and multivariable

regression models were used to compare the outcomes.

Results: Among 29,296 patients who underwent treatment for PE, 13,957 (46.7%) received ST,

13,353 (45.8%) received SCDT, and 1,986 (6.8%) received USAT. The utilization rates

of ST showed a decreasing trend from 61.6% in 2011 to 53.0% in 2022 (nptrends = -16.7,

p<0.001). On the other the utilization rates for both SCDT and USAT showed increasing

trends from 45.3% in 2011 to 47.2% in 2022 (nptrends = 3.84, p<0.001) and 2.7%% in

2011 to 10.0% in 2022 (nptrends = 5.74, p<0.001) respectively.

In-hospital mortality risks were significantly lower in USAT and SCDT compared to ST

(2.7% vs. 9.5% vs. 20.4%, p<0.001) respectively. The odds ratio of death was

significantly lower for USAT (OR: 0.11, 95% CI: 0.09 – 0.15, p<0.001) and SCDT (OR:

0.39, 95% CI: 0.36 – 0.41, p<0.001) compared to ST. At the same time, the odds ratio of

death for USAT (OR: 0.29, 95% CI: 0.22 – 0.39, p<0.001) was significantly lower than

that of SCDT.

Composite complications rates including intracranial hemorrhage, gastrointestinal

bleeding, post-procedural bleeding, anemia, need for blood transfusions, and

cardiopulmonary arrest were also lower in USAT and SCDT compared to ST (19.6% vs.

25.8% vs. 35.8%, p<0.001) respectively. The odds ratio of complications is significantly

lower in USAT (OR: 0.46, 95% CI: 0.41 – 0.51, p<0.001) and SCDT (OR: 0.61, 95% CI:

0.59 – 0.64, p<0.001) compared to ST. At the same time, the odds ratio of complications

for USAT (OR: 0.75, 95% CI: 0.67 – 0.85, p<0.001) was significantly lower than that of

SCDT. The commonest complications after each of the approaches (USAT vs. SCDT vs.

ST) were anemia (16.0% vs. 18.7% vs. 21.3%, p<0.001), need for blood transfusions

(3.3% vs. 6.2% vs. 10.2%, p<0.001), and cardiopulmonary arrest (1.1% vs. 4.3% vs.

11.6%, p<0.001) respectively.

The overall mean length of hospital stay was 7.3 ± 8.7 days and showed a significant

decrease from 8.2 ± 8.9 days in 2011 to 7.2 ± 9.0 days in 2022 (nptrends: - 13.92,

p<0.001). The mean length of hospital stay was significantly lower in both the USAT

(5.4 days vs. 7.9 days, p<0.001) and SCDT (6.9 days vs. 7.9 days, p<0.001) groups

compared to the ST groups. The median hospitalization costs were significantly lower for

USAT ($120,137 vs. $144,442, p<0.001) and SCDT ($131,456 vs. $144,442, p<0.001)

compared to ST.

USAT and SCDT had significantly higher home discharge rates vs. discharge to other

facilities, compared to ST (71.6% vs. 66.7% vs. 61.3%, p<0.001) respectively. The odds

ratio of home discharge was significantly higher for USAT (OR: 1.68, 95% CI: 1.51 –

1.87, p<0.001) and SCDT (OR: 1.39, 95% CI: 1.33 – 1.44, p<0.001) compared to ST. At

the same time, the odds ratio of home discharge for USAT (OR: 1.21, 95% CI: 1.08 –

1.35, p=0.001) was significantly higher than that of SCDT. Moreover, we found

significant regional differences regarding the use of each PE treatment approaches, with

the West having the lowest rates of USAT and the Northeast the lowest rates of SCDT.

Conclusions: Among patients hospitalized for PE treatment, USAT and SCDT lead to lowest

perioperative mortality, morbidity, length of stay, and cost than ST. Despite these

reported advantages, there are significant regional differences with respect to PE

treatment options suggesting the need to promote the standardization of best practices.

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