Relation of Duration of Symptoms With Response to Thrombolytic Therapy in Pulmonary Embolism

doi:10.1016/S0002-9149(97)00315-9

The American Journal of Cardiology

Volume 80, Issue 2, 15 July 1997, Pages 184-188

https://doi.org/10.1016/S0002-9149(97)00315-9 Get rights and content

Abstract

Five previous trials of pulmonary embolism (PE) thrombolysis showed individually that duration of symptoms did not affect lung scan reperfusion or angiographic clot lysis. We conducted an overview of 308 patients from these trials. Using 262 pairs of pre- and postlysis lung scans and 222 pairs of angiograms, we evaluated the relation between duration of PE symptoms and changes in reperfusion and/or clot lysis following thrombolysis. When comparing baseline and 24-hour post-thrombolysis lung scans, 77% of patients overall demonstrated improvement, including 69% who were treated 6 to 14 days after onset of symptoms. We detected an inverse relation between duration of symptoms and improvement on post-treatment lung scan reperfusion scores. For each additional day of symptoms before PE thrombolysis, there was a decrement of 0.8% of lung tissue reperfusion on lung scanning (95% confidence interval [CI], 0.2% to 1.4%, p = 0.008). Adjustment for age and baseline lung scan defect had little effect on the results. Similarly, on angiography, less clot lysis immediately following thrombolysis was observed in the group of patients with the longest duration of symptoms compared with those with the shortest symptom duration (mean = 1.0 score unit of angiographic improvement in those with symptoms for ≥6 days vs 1.7 score units for ≤1 day of symptoms, p = 0.03). This inverse relation between duration of symptoms and response to thrombolysis indicates that thrombolytic treatment should commence as soon as possible after PE is diagnosed. However, thrombolysis is still useful in patients who have had symptoms for 6 to 14 days.

Section snippets

Methods

Data from 5 multicenter trials of thrombolytic therapy for PE1, 2, 3, 4, 5, 6, 7that occurred between 1985 and 1994 were combined to create the database used in this overview. Of the 373 patients, 55 in the fourth trial were excluded from this analysis because they were randomized to receive heparin alone. An additional 6 patients were excluded because they did not actually receive a thrombolytic agent despite their randomization assignment to thrombolysis. Four patients who lacked data about

Patient Profile

Of the 308 patients, the mean duration of PE symptoms before thrombolysis was 3.7 ± 0.2 days. The mean age of patients was 58 years (range 18 to 86). Initial lung scans in 262 patients showed a mean perfusion defect of 41 ± 1%. Twenty-four hours after the initiation of thrombolysis, the lung scans showed a mean perfusion defect of 29 ± 1%, representing an absolute mean improvement in perfusion of 12 ± 1%. Initial quantitative angiographic scores in 222 patients showed a mean angiographic score

Discussion

With each additional day of PE symptoms, there was a small decrement in the efficacy of thrombolysis, as assessed by lung scan reperfusion and angiographic improvement. Nevertheless, substantial benefit extended to 14 days after symptom onset.

The Urokinase Pulmonary Embolism Trial[10]of 82 thrombolysis patients examined the effects of PE symptom duration on the efficacy of thrombolysis. Results indicated that urokinase treatment, assessed by lung scanning, was more effective in those with

Acknowledgements

Dr. Goldhaber received support from the Academic Award in Systemic and Vascular Medicine Grant HL 02663 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland.

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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.
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Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center
2024, Revista Portuguesa de Cardiologia
Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce.
To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes.
In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan–Meier method. Differences stratified by reperfusion were assessed using the log-rank test.
Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7–52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2–87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4–42.9, p=0.020). At a mean follow-up of 2.5 ± 3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE.
In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.
A reperfusão é geralmente o tratamento recomendado no tromboembolismo pulmonar de alto risco (TEP-AR), embora vários estudos populacionais reportem a sua subutilização. Em Portugal, não existem dados sobre incidência, tratamento e eventos nesta população.
Estimar a taxa de reperfusão na população com TEP-AR, os motivos de não reperfusão (NR) e o seu impacto nos resultados clínicos destes doentes (dts).
Coorte retrospetiva de dts consecutivos com TEP-AR num centro de referência (2008 a 2018). Os preditores independentes de NR foram estudados através de regressão logística multivariada. As incidências de mortalidade relacionada com TEP e de MACE no seguimento (morte cardiovascular, recorrência de TEP e hipertensão pulmonar tromboembólica crónica) foram calculadas pelo método de Kaplan-Meier. As diferenças entre grupos de reperfusão foram estratificadas pelo teste log-rank.
De 1955 dts com TEP agudo, 3,8% apresentaram-se hemodinamicamente instáveis. A taxa de reperfusão total foi 50% - 35 dts com trombólise sistémica, 1 dt com embolectomia percutânea primária e 1 dt com tratamento endovascular de recurso. Os preditores independentes de NR foram: idade, ter > 75 anos associou-se a 12 vezes mais risco de NR (OR 11,9, 95%CI 2,7-52,3, p=0,001); contraindicações absolutas para trombólise (31,1%), sendo a cirurgia major recente e a doença do sistema nervoso central as causas mais comuns (OR 16,7, IC95% 3,2-87,0, p<0,001); estar hospitalizado (OR 7,7, 95%CI 1,4-42,9, p=0,020). Com um seguimento médio de 2,5±3,3 anos, a sobrevida foi de 33,8%. Apesar de o impacto na mortalidade intra-hospitalar não ter atingido significado estatisticamente significativo. O grupo da reperfusão mostrou uma melhoria significativa da mortalidade aos 30 dias, 12 meses e no seguimento (com uma redução de risco relativo de 64% na mortalidade a 12 meses, p=0,013). Os resultados na redução de MACE foram semelhantes.
Na população analisada, a terapêutica recomendada de reperfusão foi registada em apenas 50% dos doentes, sendo a idade avançada e a presença de contraindicações absolutas para fibrinólise os principais preditores de não tratamento. Neste estudo, a subutilização de trombólise associou-se a um aumento significativo de mortalidade e eventos cardiovasculares a curto e longo prazo.
Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: results of a multicenter randomized RE-SPIRE trial
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Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT).
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The prognostic value of time from symptom onset to thrombolysis in patients with pulmonary embolism
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Citation Excerpt :
Although, there is a clear consensus in the emergency use of thrombolytic therapy, there is not a clearly defined ideal time of thrombolysis. Despite the short therapeutic window in acute myocardial infarction and ischemic stroke, thrombolysis might be administered during the 14 days after the beginning of symptoms in PE according to available literatures [1,4–6]. According to more recent studies, despite this longer therapeutic window, the patients who received early thrombolytic therapy in first 5 days had better outcomes [1,2,7,8].
According to clinical practice guidelines, thrombolysis can be administered during the 14 days after the beginning of symptoms in PE. However, the role of the early thrombolysis in PE has not been comprehensively investigated. In this study we evaluated the effect of short symptom-to-thrombolysis time (STT) in these patients who received the thrombolytic therapy within the 48-h.
A total of 456 patients with pulmonary embolism who underwent thrombolytic therapy in a tertiary center were included in the current study. The patients were stratified into three groups according to STT as: <12 h (Group 1), 12 to 24 h (Group 2) and > 24 to 48 h (Group 3). In-hospital events and long-term mortality were compared between the groups.
Group 3 had higher in-hospital mortality, acute kidney injury, cardiogenic shock, asystole, and the use mechanical ventilation and 3-year mortality compared to the other two groups. The 3-year overall survival for Group 1, 2 and 3 were 82.1%, 77.7% and 25.9% respectively. According to regression analysis, a STT > 24 h was independently associated with in-hospital and long-term mortality. Group 1 and 2 had similar in-hospital outcomes and long-term mortality.
A short STT has a great importance in patients with PE who treated with thrombolytic therapy. The efficacy of systemic thrombolysis significantly drops after 24 h. Because of this situation, the period between the symptom onset and thrombolytic therapy should be kept short as much as possible.
Thrombolysis in Pulmonary Embolism: An Evidence-Based Approach to Treating Life-Threatening Pulmonary Emboli
2020, Critical Care Clinics

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Relation of Duration of Symptoms With Response to Thrombolytic Therapy in Pulmonary Embolism

Abstract

Section snippets

Methods

Patient Profile

Discussion

Acknowledgements

Lancet

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Lancet

Chest