Pulmonary Embolism

10/22/2003

Question: What do recent trials tell us about diagnosis and therapy for pulmonary embolism?

<1>

Unique Identifier:12809450

Authors: Kruip MJ. Leclercq MG. van der Heul C. Prins MH. Buller HR.

Institution: Department of Internal Medicine, St. Elisabeth Hospital, Postbus 90151, 5000 LC Tilburg, The Netherlands. evert.janssen@zonnet.nl

Title: Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies. A systematic review.[comment]. [Review] [90 refs]

Source: Annals of Internal Medicine. 138(12):941-51, 2003 Jun 17.

Abstract: BACKGROUND: Pulmonary embolism is a common clinical disorder that is associated with high morbidity and mortality if untreated. It is important to confirm or rule out the diagnosis in patients with clinical suspicion of the disease. PURPOSE: To evaluate various diagnostic strategies for excluding pulmonary embolism. DATA SOURCES: MEDLINE (1966 to February 2003), EMBASE, and DARE; study investigators; and reference lists. STUDY SELECTION: Prospective clinical outcome studies. DATA EXTRACTION: The researchers recorded the frequency of symptomatic venous thromboembolism over 3 months of follow-up in patients in whom pulmonary embolism had been excluded according to various strategies. Strategies were divided into three categories according to the number of rounds of diagnostic tests needed to exclude pulmonary embolism. DATA SYNTHESIS: 25 studies involving more than 7000 patients were included. In all referred patients, two strategies-normal results on pulmonary angiography or lung scintigraphy and normal d -dimer levels combined with low clinical probability-safely excluded pulmonary embolism (failure rates < or = 3%). In the second round of diagnostic tests, in patients who had had a nondiagnostic lung scan, both pulmonary angiography and serial leg testing for venous thrombosis were accurate and safe. When d -dimer testing combined with clinical probability was inconclusive, a normal perfusion lung scan safely excluded pulmonary embolism. Accumulating evidence shows that normal results on spiral computed tomography may also safely exclude the disease. CONCLUSIONS: Many diagnostic strategies to exclude pulmonary embolism have been evaluated in consecutive patients. Interest is likely to increase in a simple, fast strategy, starting with a normal perfusion lung scan or a combination of normal d -dimer levels and low clinical probability. After the initial round of testing, a reliable diagnostic method, such as angiography or lung scintigraphy, is warranted. [References: 90] CAS Registry/EC Number 0 (Fibrin Fibrinogen Degradation Products). 0 (fibrin fragment D).

<2>

Unique Identifier:12674745

Authors: Anonymous.

Title: Diagnosis and treatment of deep venous thrombosis and pulmonary embolism.

Source: Evidence Report: Technology Assessment (Summary). (68):1-6, 2003 Jan.

<3>

Unique Identifier:12456225

Authors: Agnelli G. Becattini C. Kirschstein T.

Institution: Sezione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna, Universita degli Studi di Perugia, Via Enrico dal Pozzo, I-06123 Perugia, Italy. agnellig@unipg.it

Title: Thrombolysis vs heparin in the treatment of pulmonary embolism: a clinical outcome-based meta-analysis.[comment].

Source: Archives of Internal Medicine. 162(22):2537-41, 2002 Dec 9-23.

Abstract: BACKGROUND: In patients with acute pulmonary embolism, thrombolysis results in a more rapid resolution of pulmonary emboli than heparin treatment. Whether this advantage results in an improved clinical outcome is unclear. We sought to perform a clinical outcome-based meta-analysis of studies comparing thrombolytic and heparin treatment in patients with pulmonary embolism. METHODS: Data concerning adverse outcome events (death, recurrent pulmonary embolism, and major bleeding events) were extracted from the identified randomized studies. RESULTS: A total of 56 (23.2%) of 241 patients treated with thrombolytic agents in 9 randomized trials experienced an adverse outcome event compared with 57 (25.9%) of 220 patients treated with heparin (relative risk [RR], 0.9; 95% confidence interval [CI], 0.57-1.32). In the thrombolysis group, 11 patients (4.6%) died compared with 17 (7.7%) in the heparin group (RR, 0.59; 95% CI, 0.27-1.25). Thirty-one patients (12.9%) undergoing thrombolysis had a major bleeding episode compared with 19 patients (8.6%) treated with heparin (RR, 1.49; 95% CI, 0.85-2.81). Five fatal bleeding episodes (2.1%) occurred in the thrombolysis group and none in the heparin group. Six studies provided data on recurrent pulmonary embolism. A recurrence occurred in 14 (6.6%) of 214 patients treated with thrombolytic agents and in 22 (10.9%) of 201 patients treated with heparin (RR, 0.60; 95% CI, 0.29-1.15). Recurrence and/or death occurred in 25 (10.4%) of 241 and in 38 (17.3%) of 220 patients treated with thrombolytic agents and heparin, respectively (RR, 0.55; 95% CI, 0.33-0.96; P =.03). CONCLUSIONS: In patients with pulmonary embolism, thrombolysis had a lower composite end point of death/recurrence than heparin treatment. Excessive bleeding is the trade-off for improved efficacy. A comparative clinical outcome trial of thrombolysis and heparin treatment is warranted in patients with pulmonary embolism and selected for high risk of death and/or recurrence and low risk of bleeding. CAS Registry/EC Number 0 (Anticoagulants). 9005-49-6 (Heparin).

<4>

Unique Identifier:12427420

Authors: Thabut G. Thabut D. Myers RP. Bernard-Chabert B. Marrash-Chahla R. Mal H. Fournier M.

Institution: Service de Pneumologie et Reanimation Respiratoire, Hopital Beaujon, 100 avenue du General Leclerc, 92110 Clichy, France. gabriel.thabut@bjn.ap-hop-paris.fr

Title: Thrombolytic therapy of pulmonary embolism: a meta-analysis.

Source: Journal of the American College of Cardiology. 40(9):1660-7, 2002 Nov 6.

Abstract: OBJECTIVES: We sought to assess the efficacy and safety of thrombolytic therapy in patients with an acute pulmonary embolism (PE). BACKGROUND: Thrombolytic therapy is approved for the treatment of acute PE; however, the safety and efficacy of this therapy remain debated. METHODS: A meta-analysis of randomized, controlled trials comparing thrombolytic agents with intravenous heparin in patients with acute PE was performed. Trials were identified through a combined search of the MEDLINE, EMBASE, and Current Contents databases. Three outcome measures were assessed: 1) mortality, 2) recurrence of PE, and 3) major hemorrhage. RESULTS: Nine trials including 461 patients were identified. Compared with intravenous heparin, thrombolytic therapy had no significant effect on mortality (relative risk [RR] 0.63, 95% confidence interval [CI] 0.32 to 1.23) or the recurrence of PE (RR 0.59, 95% CI 0.30 to 1.18), but was associated with an increased risk of major hemorrhage (RR 1.76, 95% CI 1.04 to 2.98). These results were homogeneous and largely unaffected by the formulation of thrombolytic agent, the clinical severity of PE, the extent of vascular obstruction determined radiologically, or the methodologic quality of the included trials. CONCLUSIONS: Compared with intravenous heparin, thrombolytic therapy does not appear to have therapeutic benefit in unselected patients with acute PE, but it is associated with an increased risk of major hemorrhage. Given the small number of patients included in the randomized trials thus far, the negative results in terms of the efficacy outcomes should be interpreted with caution. Definitive evidence of the utility of thrombolytic therapy in this setting requires a large, randomized, controlled trial. CAS Registry/EC Number 0 (Fibrinolytic Agents). 9005-49-6 (Heparin). EC 3-4 (Streptokinase). EC 3-4-21 (Plasminogen Activators). EC 3-4-21-73 (Urinary Plasminogen Activator).

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Unique Identifier:10651604

Authors: Rathbun SW. Raskob GE. Whitsett TL.

Institution: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.

Title: Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review.[comment].

Source: Annals of Internal Medicine. 132(3):227-32, 2000 Feb 1.

Abstract: PURPOSE: To determine the sensitivity and specificity of helical computed tomography (CT) for the diagnosis of pulmonary embolism and to determine the safety of withholding anticoagulant therapy in patients who have clinically suspected pulmonary embolism and negative results on helical CT. DATA SOURCES: The MEDLINE database was searched for all reports published from 1986 to October 1999 that evaluated the use of helical CT for the diagnosis of pulmonary embolism. Bibliographies of the retrieved articles were cross-checked to identify additional studies. STUDY SELECTION: All prospective English-language studies were selected. Retrospective studies, review articles, and case reports were excluded, and 5 of the 20 identified articles were excluded. The scientific validity of the remaining 15 articles was assessed. DATA EXTRACTION: Two of the authors used a priori, pre-defined criteria to independently assess each study. A third author resolved disagreements by adjudication. The pre-defined criteria were inclusion of a consecutive series of all patients with suspected pulmonary embolism, inclusion of patients with and those without pulmonary embolism, a broad spectrum of patient characteristics, performance of helical CT and pulmonary angiography (or an appropriate reference test) in all patients, and independent interpretation of the CT scan and pulmonary angiogram (or reference test). Specific data on sensitivity and specificity and the associated 95% CIs were recorded when available. DATA SYNTHESIS: No study met all of the predefined criteria for adequately evaluating sensitivity and specificity. The reported sensitivity of helical CT ranged from 53% to 100%, and specificity ranged from 81% to 100%. In no prospective study was anticoagulant therapy withheld without further testing for venous thromboembolism in consecutive patients with suspected pulmonary embolism. One prospective study reported the outcome of selected patients with negative results on helical CT who did not receive anticoagulant therapy. CONCLUSIONS: Use of helical CT in the diagnosis of pulmonary embolism has not been adequately evaluated. The safety of withholding anticoagulant treatment in patients with negative results on helical CT is uncertain. Definitive large, prospective studies should be done to evaluate the sensitivity, specificity, and safety of helical CT for diagnosis of suspected pulmonary embolism. CAS Registry/EC Number 0 (Anticoagulants).

<6>

Unique Identifier:10378570

Authors: Arcasoy SM. Kreit JW.

Institution: Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, USA. arcasoy@mail.med.upenn.edu

Title: Thrombolytic therapy of pulmonary embolism: a comprehensive review of current evidence. [Review] [102 refs]

Source: Chest. 115(6):1695-707, 1999 Jun.

Abstract: Pulmonary embolism (PE) is a common disorder that is accompanied by significant morbidity and mortality. Although anticoagulation is the standard treatment for PE, thrombolytic therapy, with its ability to produce rapid clot lysis, has long been considered an attractive alternative. Although many studies have been performed over the past three decades, however, the indications for the use of thrombolytic agents in patients with PE remain controversial. In this article, we review the medical literature and provide evidence-based guidelines for the use of thrombolytic therapy. We will also discuss the practical aspects of PE thrombolysis. [References: 102] CAS Registry/EC Number 0 (Anticoagulants). 0 (Fibrinolytic Agents).

<7>

Unique Identifier:8054013

Authors: Anonymous.

Institution: ICRF/BHF/MRC Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford.

Title: Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.[comment].

Source: BMJ. 308(6923):235-46, 1994 Jan 22.

Abstract: OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered. CAS Registry/EC Number 0 (Platelet Aggregation Inhibitors).

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