Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage

Chatterjee, Saurav; Chakraborty, Anasua; Weinberg, Ido; Kadakia, Mitul B.; Wilensky, Robert L.; Sardar, Partha; Kumbhani, Dharam J.; Mukherjee, Debabrata; Jaff, Michael R.; Giri, Jay

doi:10.1001/jama.2014.5990

Cited by 620 publications

(211 citation statements)

References 41 publications

(25 reference statements)

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“…A recent meta-analysis showed a 1.7% absolute mortality benefit with systemic fibrinolysis versus anticoagulation alone in submassive PE, but this was achieved with the cost of a 6% absolute increase in the rate of major bleeding, including a 1.5% rate of intracranial hemorrhage. 5 The intracranial hemorrhage rate with systemic fibrinolysis has been estimated to be 3% in the real-world experience of the International Cooperative Pulmonary Embolectomy Registry, which included all patients with acute PE. 6 Fear of the risk of intracranial hemorrhage associated with systemic fibrinolysis has driven strong interest in alternative therapies to rapidly relieve RV pressure overload, while minimizing the risk of intracranial hemorrhage.…”

Section: Introductionmentioning

confidence: 99%

Surgical Pulmonary Embolectomy

et al. 2015

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A 66-year-old man with a recent prosthetic knee infection, status postprosthesis removal, was admitted with recurrent septic arthritis. On his seventh hospital day, as he was signing his discharge paperwork, he developed acute respiratory distress. On physical examination, he was tachycardic to 118 beats/min, relatively hypotensive from 144/78 mm Hg earlier in the day to 94/54 mm Hg, and hypoxemic, with an oxygen saturation of 94% on a 100% nonrebreather facemask. The ECG showed sinus tachycardia. An urgent contrast-enhanced chest computed tomogram (CT) demonstrated large saddle pulmonary embolism (PE) and severe right ventricular (RV) enlargement, with an RV diameterto-left ventricular (LV) diameter ratio of 1.8 (Figure 1). The patient was administered a bolus of intravenous unfractionated heparin followed by a continuous infusion. An urgent bedside transthoracic echocardiogram showed severe RV dilation, moderateto-severe pulmonary hypertension, and RV pressure overload as suggested by systolic deviation of the interventricular septum toward the LV (Figure 2). The Vascular Medicine and Cardiac Surgery services were consulted for consideration of advanced therapies. Because of concern for major bleeding associated with fibrinolytic therapy in the setting of recent major surgery, surgical pulmonary embolectomy was recommended. IntroductionDespite advances in diagnostics and therapeutics, acute PE remains a life-threatening condition with an in-hospital mortality rate of ≈7% for all-comers and 31% for patients with hemodynamically unstable (massive) PE.1 Current management algorithms emphasize risk stratification to identify patients who may benefit from early advanced therapies in addition to anticoagulation.2-4 Risk categories of massive, submassive, and low-risk PE are based on clinical, radiological, and laboratory criteria. Massive PE is characterized by systemic arterial hypotension, syncope, cardiogenic shock, cardiac arrest, or respiratory failure. Submassive PE is defined by evidence of RV dysfunction on imaging (RV/LV diameter >0.9 on contrastenhanced chest CT or RV dilation and hypokinesis on echocardiography), elevated cardiac biomarkers (such as cardiac troponin), or both, in a patient with preserved systemic arterial pressure. Submassive PE comprises a patient population at increased risk of adverse outcomes and early mortality. Low-risk PE patients have none of these features and typically have an uneventful clinical course when treated with therapeutic anticoagulation alone.Advanced therapies are often considered for patients with submassive or massive PE to rapidly relieve RV pressure overload and avert hemodynamic deterioration. Advanced therapies for reperfusion include systemic fibrinolysis, catheter-based pharmacomechanical intervention, and surgical pulmonary embolectomy. A recent meta-analysis showed a 1.7% absolute mortality

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Section: Introductionmentioning

confidence: 99%

Surgical Pulmonary Embolectomy

et al. 2015

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“…53 Another meta-analysis evaluated four studies and 1,775 patients with submassive PTE, observing a 3.9% reduction in mortality in the heparin arm and a 2.2% reduction with SFT, which was due to an increase in major bleeding from 3.4 to 9.2% with SFT. 12 Two other recent metanalyses reported similar results. 54,55 However, the only two studies that assessed patients over the long term demonstrated that PH reduced with SFT.…”

Section: Patients With Submassive Pte (Moderate Risk)mentioning

confidence: 59%

“…35 A systematic review of randomized studies of SFT for PTE demonstrated an incidence of 9.24% of major bleeding in 2,115 patients vs. 1.45% in the heparin arm. 12 The Pulmonary Embolism Thrombolysis study (PEITHO) observed 11.5% major bleeding with SFT vs. 2.5% with heparin. When compared on the basis of CNS bleeding, the rates were 2 and 0.2% respectively.…”

Section: Risk Of Bleeding With Systemic Fibrinolytic Agentsmentioning

confidence: 99%

“…42 This extensive list of risk factors and contraindications excludes 50% of PTE patients from SFT, although in certain special cases its use can still be considered. 12 Bleeding while on SFT is still a subject of debate, and options such as reducing the recommended dose in bolus and local administration with catheters (pharmaco-mechanical thrombolysis) are already being used and have begun to exhibit promising results.…”

Section: Risk Of Bleeding With Systemic Fibrinolytic Agentsmentioning

confidence: 99%

“…11 Naturally, one of the most significant problems related to use of SFT is the increased number of major bleeding events (10 to 20%), particularly in the central nervous system (CNS), with morbidity, including mortality, of up to 55%, which obviously limits its benefits. 12,13 As a result, current consensus statements on management of PTE are clear and objective in stating that the only precise indication for using SFT is in patients with HI. 3,14,15 The ninth consensus of the American College of Chest Physicians (ACCP), in 2012, suggested that SFT should only be used in the absence of HI in severe PTE with RV failure and even this recommendation was based on a very weak evidence level (2C) and was subject to case-by-case assessment of risks and benefits.…”

Section: Introductionmentioning

confidence: 99%

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Terapia fibrinolítica sistêmica no tromboembolismo pulmonar

Ceresetto

Marques

2017

J. vasc. bras.

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Pulmonary thromboembolism remains a major therapeutic challenge for specialists and, despite investment and the consequent developments in diagnosis, prophylaxis, and treatment, the condition is still the leading cause of avoidable deaths in hospital settings. There is still great uncertainty with relation to the profile of patients who will actually benefit from systemic fibrinolytic treatment, without being exposed to serious risk of bleeding. There are tools that can help to identify patients who will benefit, including risk stratification and estimation of the prognosis of the event, with clinical scores for right ventricular failure, markers of right ventricular dysfunction and dilatation, and thrombotic mass assessment, whether alone or in combination. The only points of consensus with relation to fibrinolytic therapy for treatment of pulmonary thromboembolism are as follows: it should not be routinely indicated, none of the scores or markers alone should be used to justify its use, and patients with hemodynamic instability are the most likely to benefit. Furthermore, each case should be evaluated for risk of bleeding, especially central nervous system bleeding.Keywords: fibrinolytics; pulmonary embolism; hemorrhage. ResumoO tromboembolismo pulmonar permanece como um grande desafio terapêutico para os médicos especialistas, pois, apesar de todo investimento e desenvolvimento em seu diagnóstico, profilaxia e tratamento, essa condição continua sendo a principal causa de morte evitável em ambiente hospitalar. Ainda restam muitas dúvidas em relação a qual perfil de paciente vai se beneficiar de fato da terapia fibrinolítica sistêmica, sem ficar exposto a um grande risco de sangramento. A estratificação de risco e a avaliação do prognóstico do evento, através de escores clínicos de insuficiência ventricular direita, marcadores de dilatação e disfunção do ventrículo direito e avaliação da massa trombótica, associados ou de forma isolada, são ferramentas que podem auxiliar na identificação do paciente que irá se beneficiar dessa terapia. Os únicos consensos em relação à terapia fibrinolítica no tratamento do tromboembolismo pulmonar são: não deve ser indicada de forma rotineira; nenhum dos escores ou marcadores, isoladamente, devem justificar seu uso; e os pacientes com instabilidade hemodinâmica são os mais beneficiados. Além disto, deve-se avaliar cada caso em relação ao risco de sangramento, especialmente no sistema nervoso central.Palavras-chave: fibrinolíticos; embolia pulmonar; hemorragia.

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