Lisa K. Moores, MD; William L. Jackson Jr., MD; Andrew F. Shorr, MD, MPH; Jeffrey L. Jackson, MD, MPH
Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Department of the Army or the U.S. Department of Defense.
Acknowledgments: The authors thank Christopher Bennett, MD, for his expertise with CTPA and Mr. Robert J. Mohrman for his assistance with the literature search.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Lisa K. Moores, MD, Uniformed Services University of the Health Sciences, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307; e-mail, Lisa.Moores@na.amedd.army.mil.
Current Author Addresses: Drs. Moores, W.L. Jackson, and Schorr: Uniformed Services University of the Health Sciences, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307.
Dr. J.L. Jackson: Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814.
Spiral computed tomographic pulmonary angiography (CTPA) is increasingly being used in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, CTPA as a definitive diagnostic test may be limited by inadequate sensitivity, especially in instances of isolated subsegmental emboli.
To assess the safety of withholding anticoagulation in patients with suspected PE and negative results on CTPA.
All relevant studies identified in MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) and in bibliographies of key articles. The search was not limited to the English language.
The authors selected all published studies that used CTPA to evaluate suspected PE and reported at least 3 months of follow-up in patients not receiving anticoagulation on the basis of a negative CTPA result.
Two reviewers independently rated study quality on the basis of predetermined criteria. Data were extracted on participants, CTPA technique, diagnostic studies performed, prevalence of PE, number of patients with negative or indeterminate CTPA results who were followed, and subsequent rates of venous thromboembolism and fatal PE.
Twenty-three studies reported on 4657 patients with negative CTPA results who did not receive anticoagulation. The 3-month rate of subsequent venous thromboembolic events was 1.4% (95% CI, 1.1% to 1.8%), and the 3-month rate of fatal PE was 0.51% (CI, 0.33% to 0.76%).
The CTPA technology used varied across studies and was not applied uniformly in the same step of diagnostic algorithms. Only 1 study used CTPA as the sole diagnostic test.
The rate of subsequent venous thromboembolism after negative results on CTPA is similar to that seen after negative results on conventional pulmonary angiography. It appears to be safe to withhold anticoagulation after negative CTPA results.
Is it safe to withhold anticoagulation in adults with suspected pulmonary embolism (PE) and negative results on spiral computed tomographic pulmonary angiography (CTPA)?
This meta-analysis summarized data from 23 studies that reported rates of thromboembolism among patients with suspected PE who did not receive anticoagulation after negative results on CTPA. Among 4657 patients, the 3-month risks for a thromboembolic event and fatal PE were 1.4% and 0.51%, respectively.
Studies used early-generation CT technology and different diagnostic algorithms for thromboembolism.
Withholding anticoagulation from patients with low to moderate probability of PE and negative results on CTPA appears reasonable.
Flow diagram of study selection.
Table. Data Extracted from Individual Studies
Appendix Table. Quality Ratings of Included Studies
Forest plots of total venous thromboembolism (VTE) events (top) and fatal pulmonary embolism (PE) events (bottom).
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Shaun D Frost
HealthPartners Medical Group and Clinics, Minneapolis, MN
December 7, 2004
Using CTPA to Diagnose Pulmonary Embolism
I am concerned that the article by Moores and colleagues (1) conveys an ambiguous message about the utility of spiral computed tomographic pulmonary angiography (CTPA) for diagnosing pulmonary embolism (PE). The ambiguity results from seemingly different conclusions in the abstract, discussion, and editors' synopsis sections of the manuscript. The authors conclude their discussion by stating that withholding anticoagulation seems to be safe in patients managed by negative results on CTPA performed concurrently with imaging of the lower extremities (either ultrasonography or CT venography). The abstract that accompanies the manuscript however fails to mention the importance of concurrent lower extremity imaging, stating only "it appears to be safe to withhold anticoagulation after negative CTPA results." The editors' synopsis also fails to mention lower extremity imaging, yet adds that concurrent clinical probability assessment is necessary by stating "withholding anticoagulation from patients with low to moderate probability of PE and negative results on CTPA appears reasonable".
These incongruences are not trivial. Given that busy clinicians often only read the abstract and editors' synopsis sections of a manuscript, every effort should be made to ensure that these sections accurately reflect the authors' conclusions. As this pertains to the article by Moores and colleagues, clinicians who read only the abstract may conclude that a negative CTPA can function as the sole diagnostic test for ruling out PE. Diagnostic strategies based on this erroneous conclusion will exclude lower extremity imaging and clinical probability estimation, and subsequently some patients with venous thrombosis may not be diagnosed or treated.
References 1. Moores L, Jackson W, Shorr A, Jackson J. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med. 2004;141:866-874.
Institut Mutualiste Montsouris, Paris, France
December 11, 2004
CT pulmonary angiography and suspected pulmonary embolism: a word of caution
In their careful and commendable meta-analysis of outcome studies that used CT pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE), Moores and colleagues conclude that "it appears to be safe to withhold anticoagulation after negative CTPA results". I believe that such a message goes beyond the conclusions that can be drawn from the authors' data. As acknowledged by the authors, among the 23 outcome studies they analyzed, only one used CTPA as the sole diagnostic test. Further, in the three largest prospective studies (at least 350 patients in each study remained untreated), anticoagulation was withheld only when both CTPA and compression ultrasonography (CUS) of the lower limbs were negative(1-3). When it could be calculated, the prevalence of DVT detected by CUS in patients with negative CTPA results was very low (0.8%) in one study (3), but it was significantly higher in 2 other studies (7.7% and 8.4%, respectively(1, 4)), and it reached 18.8% in a study of 117 hospitalized patients(5). Therefore, until specific outcome studies demonstrate the opposite, using CTPA as the sole diagnostic test to withhold anticoagulation in patients with suspected PE should be considered unwise, not "safe".
1. Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet. 2002;360(9349):1914-1920. 2. Perrier A, Roy PM, Aujesky D, et al. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med. 2004;116(5):291-9. 3. van Strijen MJ, de Monye W, Schiereck J, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med. 2003;138(4):307-14. 4. Perrier A, Howarth N, Didier D, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001;135(2):88-97. 5. Bourriot K, Couffinhal T, Bernard V, Montaudon M, Bonnet J, Laurent F. Clinical outcome after a negative spiral CT pulmonary angiographic finding in an inpatient population from cardiology and pneumology wards. Chest. 2003;123(2):359-65.
Pieter W. Kamphuisen
Division of Internal and Cardiovascular Medicine, University of Perugia, Italy
December 24, 2004
CT Pulmonary Angiography should be part of a diagnostic strategy for pulmonary embolism.
Contrast-enhanced spiral computed tomography (CTPA) is becoming the preferred diagnostic test for suspected acute pulmonary embolism (PE) in many hospitals. Based on their meta-analysis Moores et al. (1) conclude that it appears to be safe to withhold anticoagulant therapy after a negative CTPA in patients with suspected PE. This may imply that CTPA could be used as the first and sole diagnostic test in these patients. We believe that this conclusion is premature for two different reasons. First, in consecutive patients with suspected PE the sensitivity of CTPA is only 70% and the negative likelihood ratio is 0.3 (2). This likelihood ratio is comparable to that of a low probability lung scan, a diagnostic result considered insufficient to safely exclude PE. The sensitivity of CTPA is only 30% for detection of isolated subsegmental emboli (3). These isolated subsegmental emboli are present in up to 30% of patients with documented PE and their clinical significance cannot be excluded. Second, CTPA should be part of a diagnostic strategy for the diagnosis of PE and not be the sole diagnostic test. The combination of a low clinical probability score and a normal d-dimer level has been shown to safely exclude PE in 20-30% of patients (4). Therefore, using such an approach will prevent 20-30% of the patients from further diagnostic testing. Placing CTPA in the second round of a diagnostic strategy will reduce costs and radiation exposure. The low risk patients will be filtered by a highly accurate, simple and cheap strategy. In the remaining high risk patients, including patients with high d-dimer levels or high clinical probability, CTPA can be performed to confirm the diagnosis of PE or establish an alternative diagnosis. Thus, since the diagnostic accuracy of excluding PE using CTPA seems sub- optimal and this test is relatively expensive, CTPA should not be used as the first diagnostic test in patients with suspected PE, but must be implemented in a diagnostic strategy, which begins with clinical probability and d-dimer assessment.
1. Moores LK, Jackson Jr. WL, Shorr AF, Jackson JL. Meta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography. Ann Intern Med 2004;141:866- 874. 2. Perrier A, Howarth N, Didier D, Loubeyre P, Unger PF, de Moerloose P, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med 2001;135:88- 97. 3. Goodman LR, Curtin JJ, Mewissen MW, Foley WD, Lipchik RJ, Crain MR, et al. Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography. AJR Am J Roentgenol 1995;164:1369-74. 4. Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, et al. D- dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004;140:589-602.
Jeremy P Smith
January 20, 2005
The Applicability of a Negative Computed Tomographic Pulmonary Angiogram in Clinical Practice
Moores and colleagues state in their discussion that "Our data suggest that it is safe to withhold anticoagulation in patients with negative results on CTPA." There are two problems with this conclusion. The first is that almost all the studies included in the meta-analysis involved additional testing before discharging patients without anticoagulation, e.g. negative Duplex ultrasonography or non-diagnostic ventilation/perfusion scans. These results would serve to create a pool of patients with lower likelihood of occult PE as compared to patients who had simply one negative CTPA. One therefore cannot derive, from this data, the conclusion that it is safe to withhold anticoagulation in patients with negative CTPA in the absence of additional testing.
The second problem is that a significant percentage of patients in these studies did receive anticoagulation, occasionally because the clinical probability for PE remained high despite a negative CTPA. Moores and colleagues exclude these patients from their analysis of outcomes, but one cannot then extrapolate from this outcome data that it is safe to withhold anticoagulation in patients with negative CTPA. The only safe conclusion would be that it is safe to withhold anticoagulation in patients with negative CTPA who have no other indication for anticoagulation (including high suspicion of PE).
Lisa K Moores
Uniformed Services University of the Health Sciences
February 8, 2005
Defining the Role of CTPA in Suspected Pulmonary Embolism
IN RESPONSE: We appreciate the comments regarding our meta-analysis (1) and the opportunity to clarify our conclusion. As stated in the discussion, "the role of CTPA without concomitant lower-extremity imaging is still undefined" (1). We agree with both Dr. Frost and Dr. Girard that the literature to date does not support definitive exclusion of VTE with CTPA alone, and we recommend concurrent lower-extremity imaging before withholding anticoagulation in patients with suspected clot. While advancements in imaging technology may eventually improve diagnostic accuracy of CTPA and allow for a single test, in our opinion further study is required before this can be recommended. Moreover, the emergence of simultaneous CT venography might ultimately permit rapid, accurate assessment of the lower extremities in a combined, single-modality study (2-5), rendering moot the role of isolated imaging of the chest in VTE. We agree with both Dr. Frost and Dr. Girard that our abstract should have been written more explicitly to match our ultimate conclusions.
In response to Dr. Kamphuisen, we did not endorse CTPA as an initial diagnostic test. On the contrary, we acknowledged that "pretest probability assessments should be used to select patients for CTPA, since recent publications support the exclusion of PE based on a low pretest probability and negative results on D-dimer testing" (1).
William L. Jackson, Jr., MD Lisa K. Moores, MD Walter Reed Army Medical Center Washington, DC 20307
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
1. Moores LK, Jackson WL Jr, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomography pulmonary angiography. Ann Intern Med 2004;141:866- 874.
2. Loud PA, Katz DS, Bruce DA, Klippenstein DL, Grossman ZD. Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001;219:498- 502.
3. Cham MD, Yankelevitz DF, Shaham D, Shah AA, Sherman L, Lewis A, et al. Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group. Radiology. 2000;216:744-51.
4. Ghaye B, Dondelinger RF. Non-traumatic thoracic emergencies: CT venography in an integrated diagnostic strategy of acute pulmonary embolism and venous thrombosis. Eur Radiol. 2002;12:1906-21.
5. Lim KE, Hsu YY, Hsu WC, Huang CC. Combined computed tomography and venography and pulmonary angiography for the diagnosis of PE and DVT in the ED. Am J Emerg Med. 2004;22:301-6.
Moores LK, Jackson WL, Shorr AF, Jackson JL. Meta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography. Ann Intern Med. ;141:866–874. doi: 10.7326/0003-4819-141-11-200412070-00011
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Published: Ann Intern Med. 2004;141(11):866-874.
Emergency Medicine, Pulmonary Embolism, Pulmonary/Critical Care, Venous Thromboembolism.
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