Thrombolytic Therapy in Unstable Patients with Acute Pulmonary Embolism: Saves Lives but Underused

doi:10.1016/j.amjmed.2011.10.015

The American Journal of Medicine

Volume 125, Issue 5, May 2012, Pages 465-470

https://doi.org/10.1016/j.amjmed.2011.10.015 Get rights and content

Abstract

Background

Data are sparse and inconsistent regarding whether thrombolytic therapy reduces case fatality rate in unstable patients with acute pulmonary embolism. We tested the hypothesis that thrombolytic therapy reduces case fatality rate in such patients.

Methods

In-hospital all-cause case fatality rate according to treatment was determined in unstable patients with pulmonary embolism who were discharged from short-stay hospitals throughout the United States from 1999 to 2008 by using data from the Nationwide Inpatient Sample. Unstable patients were in shock or ventilator dependent.

Results

Among unstable patients with pulmonary embolism, 21,390 of 72,230 (30%) received thrombolytic therapy. In-hospital all-cause case fatality rate in unstable patients with thrombolytic therapy was 3105 of 21,390 (15%) versus 23,820 of 50,840 (47%) without thrombolytic therapy (P < .0001). All-cause case fatality rate in unstable patients with thrombolytic therapy plus a vena cava filter was 505 of 6630 (7.6%) versus 4260 of 12,850 (33%) with a filter alone (P < .0001). Case fatality rate attributable to pulmonary embolism in unstable patients was 820 of 9810 (8.4%) with thrombolytic therapy versus 1080 of 2600 (42%) with no thrombolytic therapy (P < .0001). Case fatality rate attributable to pulmonary embolism in unstable patients with thrombolytic therapy plus vena cava filter was 70 of 2590 (2.7%) versus 160 of 600 (27%) with a filter alone (P < .0001).

Conclusion

In-hospital all-cause case fatality rate and case fatality rate attributable to pulmonary embolism in unstable patients was lower in those who received thrombolytic therapy. Thrombolytic therapy resulted in a lower case fatality rate than using vena cava filters alone, and the combination resulted in an even lower case fatality rate. Thrombolytic therapy in combination with a vena cava filter in unstable patients with acute pulmonary embolism seems indicated.

Section snippets

Materials and Methods

Unstable patients with acute pulmonary embolism discharged from short-stay hospitals throughout the United States from 1999 to 2008 and their in-hospital mortality according to the use of thrombolytic therapy were identified from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.¹⁵

The Nationwide Inpatient Sample contains data from 5 to 8 million hospital stays from approximately 1000 hospitals. It is designed to approximate a

Results

From 1999 to 2008, 2,110,320 patients were discharged from short-stay hospitals in the United States with a diagnosis of pulmonary embolism. Among these, 72,230 (3.4%) were unstable (in shock or ventilator dependent). Among unstable patients, 21,390 (30%) received thrombolytic therapy and 50,840 (70%) did not. Associated comorbid conditions were more often present in those who did not receive thrombolytic therapy than in those who did (Table 1). The proportion of unstable patients who received

Discussion

Thrombolytic therapy in unstable patients was associated with a lower in-hospital all-cause case fatality rate and fewer deaths attributable to pulmonary embolism. Despite these reductions in case fatality rate, thrombolytic therapy was administered to only 30% of unstable patients, and the use of thrombolytic therapy in unstable patients with pulmonary embolism decreased from 1999 to 2008. Pulmonary embolectomy cannot explain the reduced use of thrombolytic therapy. Only 1.2% of unstable

Conclusions

All-cause case fatality rate and case fatality rate attributable to pulmonary embolism were lower in unstable patients with pulmonary embolism who received thrombolytic therapy than in those who did not receive thrombolytic therapy. Thrombolytic therapy was associated with a larger reduction of case fatality rate than using vena cava filters without thrombolytic therapy, and thrombolytic therapy was associated with an even lower case fatality rate when used in combination with vena cava

References (21)

N.L. Browse et al.
Streptokinase and pulmonary embolism
Lancet
(1964)
M. Levine et al.
A randomized trial of a single bolus dosage regimen a recombinant tissue plasminogen activator in patients with acute pulmonary embolism
Chest
(1990)
S. Dalla-Volta et al.
PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolismPlasminogen activator Italian multicenter study 2
J Am Coll Cardiol
(1992)
S.Z. Goldhaber et al.
Alteplase versus heparin in acute pulmonary embolism: randomized trial assessing right-ventricular function and pulmonary perfusion
Lancet
(1993)
M.E. Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)
E. Skaf et al.
Catheter embolectomy in the management of massive pulmonary embolism
Am J Cardiol
(2007)
P.D. Stein et al.
Estimated case fatality rate from pulmonary embolism, 1979-1998
Am J Cardiol
(2004)
C. Kearon et al.
Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition)
Chest
(2008)
The urokinase pulmonary embolism trial
Circulation
(1973)
D.A. Tibbutt et al.
Comparison by controlled clinical trial of streptokinase and heparin in treatment of life-threatening pulmonary embolism
Br Med J
(1974)

There are more references available in the full text version of this article.

Cited by (234)

Management of high-risk pulmonary embolism in the emergency department: A narrative review
2024, American Journal of Emergency Medicine
High-risk pulmonary embolism (PE) is a complex, life-threatening condition, and emergency clinicians must be ready to resuscitate and rapidly pursue primary reperfusion therapy. The first-line reperfusion therapy for patients with high-risk PE is systemic thrombolytics (ST). Despite consensus guidelines, only a fraction of eligible patients receive ST for high-risk PE.
This review provides emergency clinicians with a comprehensive overview of the current evidence regarding the management of high-risk PE with an emphasis on ST and other reperfusion therapies to address the gap between practice and guideline recommendations.
High-risk PE is defined as PE that causes hemodynamic instability. The high mortality rate and dynamic pathophysiology of high-risk PE make it challenging to manage. Initial stabilization of the decompensating patient includes vasopressor administration and supplemental oxygen or high-flow nasal cannula. Primary reperfusion therapy should be pursued for those with high-risk PE, and consensus guidelines recommend the use of ST for high-risk PE based on studies demonstrating benefit. Other options for reperfusion include surgical embolectomy and catheter directed interventions.
Emergency clinicians must possess an understanding of high-risk PE including the clinical assessment, pathophysiology, management of hemodynamic instability and respiratory failure, and primary reperfusion therapies.
Management of high and intermediate-high risk pulmonary embolism: A position paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology
2024, International Journal of Cardiology
Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress.
Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role.
Catheter-directed therapy for acute pulmonary embolism: results of a multicenter national registry
2024, Revista Espanola de Cardiologia
El emergente tratamiento por catéter (TPC) de la embolia pulmonar (EP) aguda combina técnicas heterogéneas. El objetivo del estudio es describir la práctica clínica contemporánea y los resultados relacionados con la TPC en un registro de ámbito nacional.
Registro multicéntrico iniciado por investigador, destinado a incluir a pacientes con EP aguda consecutivos y en riesgo intermedio-alto (IAR) o alto riesgo (AR) elegibles para TPC. El resultado primario del estudio fue la muerte por cualquier causa en el hospital.
Se incluyó en total a 253 pacientes, 93 (36,8%) con EP-AR y 160 (63,2%) con EP-IAR, de una media de edad de 62,3 ± 15,1. Se realizó trombolisis local al 70,8% de los pacientes, trombectomía aspirativa al 51,8% y ambas al 23,3%. Sin embargo, la trombectomía por aspiración fue más frecuente en la cohorte de EP-AR (el 80,6 frente al 35%; p < 0,001). Solo 51 pacientes (20,2%) se sometieron a TPC con dispositivos específicos de EP. El éxito de la TPC fue del 90,9% (el 98,1% de los casos de EP-IAR frente al 78,5% de los de EP-AR; p < 0,001). La mortalidad hospitalaria fue del 15,5%, muy concentrada en los casos de EP-AR (37,6%) y significativamente menor entre los de EP-IAR (2,5%; p < 0,001). La mortalidad a largo plazo (24 meses) fue del 40,2 en EP-AR frente al 8,2% en EP-IAR (p < 0,001).
A pesar del elevado éxito de la TPC, la mortalidad hospitalaria por EP-AR sigue siendo alta (37,6%) respeto a la muy baja mortalidad de la EP-IAR (2,5%).
Catheter-directed therapy (CDT) for acute pulmonary embolism (PE) is an emerging therapy that combines heterogeneous techniques. The aim of the study was to provide a nationwide contemporary snapshot of clinical practice and CDT-related outcomes.
This Investigator-initiated multicenter registry aimed to include consecutive patients with intermediate-high risk (IHR) or high-risk (HR), acute PE eligible for CDT. The primary outcome of the study was in-hospital all-cause death.
A total of 253 patients were included, of whom 93 (36.8%) had HR-PE, and 160 (63.2%) had IHR-PE with a mean age of 62.3 ± 15.1 years. Local thrombolysis was performed in 70.8% and aspiration thrombectomy in 51.8%, with 23.3% of patients receiving both. However, aspiration thrombectomy was favored in the HR-PE cohort (80.6% vs 35%; P < .001). Only 51 patients (20.2%) underwent CDT with specific PE devices. The success rate for CDT was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P < .001). In-hospital mortality was 15.5%, and was highly concentrated in the HR-PE patients (37.6%) and significantly lower in IHR-PE patients (2.5%), P < .001. Long-term (24-month) mortality was 40.2% in HR-PE patients vs 8.2% in IHR-PE patients (P < .001).
Despite the high success rate for CDT, in-hospital mortality in HR-PE is still high (37.6%) compared with very low IHR-PE mortality (2.5%).
Contemporary trends in mortality related to high-risk pulmonary embolism in US from 1999 to 2019
2023, Thrombosis Research
Population-based data on high-risk pulmonary embolism (PE) mortality trends in the United States (US) are scant.
To assess current trends in US mortality related to high-risk PE over the past 21 years and determine differences by sex, race, ethnicity, age and census region.
Data were extracted from the Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) to determine trends in age-adjusted mortality rates (AAMR) per 100,000 people, due to high-risk PE. To calculate nationwide annual trends, we assessed the average (AAPC) and annual percent change (APC) with relative 95 % confidence intervals (CIs) using Joinpoint regression.
Between 1999 and 2019, high-risk PE was listed as the underlying cause of death in 209,642 patients, corresponding to an AAMR of 3.01 per 100,000 people (95 % CI: 2.99 to 3.02). AAMR from high-risk PE remained stable from 1999 to 2007 [APC: −0.2 %, (95 % CI: −2.0 to 0.5, p = 0.22)] and then significantly increased [APC: 3.1 % (95 % CI: 2.6 to 3.6), p < 0.0001], especially in males [AAPC: 1.9 % (95 % CI: 1.4 to 2.4), p < 0.001 vs AAPC: 1.5 % (95 % CI: 1.1 to 2.2), p < 0.001]. AAMR increase was more pronounced in those <65 years, Black Americans, and residents of rural areas.
In an US population analysis, high-risk PE mortality rate increased, with racial, sex-based, and regional variations. Further studies are needed to understand root causes for these trends and to implement appropriate corrective strategies.
Air and Thrombotic Venous Embolism in a Department of Emergency Medicine. A Literature Review
2023, Current Problems in Cardiology
Citation Excerpt :
Some authors include the need for mechanical ventilation in this definition. Fortunately, high-risk PE is not common due to the VAE; in a retrospective study of US hospitals, only 3.4% of acute PE diagnoses were classified as high risk.26 The examples for this review had radiological evidence of gas embolism and thrombosis of the jugular and right subclavian venous system, so it was necessary to rule out pulmonary thromboembolism.
Among the different types of central venous access, 2 are mainly recognized, the internal jugular and the subclavian. The most common complications of these invasive procedures are hematoma, vascular injury, pneumothorax, and hemothorax. This review presents 2 atypical complications in the central vascular approach in a patient seen in the emergency department. Complications were air and thrombotic embolisms. Physicians dealing with central venous catheter placement (emergency department, intensive care unit, surgical room, interventionist procedures) should be aware that vascular air embolism is an iatrogenic able to be detected with imaging methods (computed tomography pulmonary angiography, magnetic resonance imaging) as strategies to minimize the risks, which even in expert hands is not exempt from the complications it can have.
Blueprint for developing an effective pulmonary embolism response network
2023, Revista Portuguesa de Cardiologia
Acute pulmonary embolism (PE) is a major cause of morbidity and mortality in Portugal. It is the third most common cause of cardiovascular death after stroke and myocardial infarction. However, the management of acute PE remains poorly standardized, and there is a lack of access to mechanical reperfusion when indicated.
This working group analyzed the current clinical guidelines for the use of percutaneous catheter-directed treatment in this setting and proposed a standardized approach for severe forms of acute PE. This document also proposes a methodology for the coordination of regional resources in order to create an effective PE response network, based on the hub-and-spoke organization design.
This model can be applied at the regional level, but it is desirable to extend it to the national level.
A embolia pulmonar aguda (EP) é uma das principais causas de morbilidade e mortalidade em Portugal. É a terceira causa mais comum de morte cardiovascular após acidente vascular cerebral e enfarte agudo do miocárdio. No entanto, o manejo da EP aguda permanece mal padronizado e falta acesso à reperfusão mecânica, quando indicada.
Este grupo de trabalho analisou as recomendações clínicas atuais para o uso de terapêutica percutânea dirigida por cateter neste cenário e propõe uma abordagem padronizada para formas graves de EP aguda. Este documento também foi redigido com o objetivo de propor uma metodologia de coordenação de recursos regionais para a criação de uma rede efetiva de resposta à EP, baseada no desenho da organização hub and spoke.
Esse modelo pode ser aplicado a nível regional, mas é desejável estendê-lo a nível nacional.

View all citing articles on Scopus

: Funding: None.

: Conflict of Interest: None.

: Authorship: All authors had access to the data and played a role in writing this manuscript.

View full text

Clinical research studyThrombolytic Therapy in Unstable Patients with Acute Pulmonary Embolism: Saves Lives but Underused

Abstract

Background

Methods

Results

Conclusion

Section snippets

Materials and Methods

Results

Discussion

Conclusions

Lancet

Chest

J Am Coll Cardiol

Lancet

J Chronic Dis

Am J Cardiol

Am J Cardiol

Chest

The urokinase pulmonary embolism trial

Circulation

Comparison by controlled clinical trial of streptokinase and heparin in treatment of life-threatening pulmonary embolism

Br Med J

Clinical research study
Thrombolytic Therapy in Unstable Patients with Acute Pulmonary Embolism: Saves Lives but Underused