ArticlesDiagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial
Introduction
The contemporary diagnostic approach of pulmonary embolism is based on the combination of clinical probability assessment of disease with sequential diagnostic tests such as plasma D-dimer measurement, venous compression ultrasonography of the leg, and helical CT.1, 2, 3 CT of the chest has emerged as a new way to directly visualise the clot in pulmonary arteries.4 First-generation single-slice spiral CT had a low sensitivity (about 70%) for pulmonary embolism,5, 6 restricting its use as a stand-alone test. Emergence of multislice CT (MSCT) has renewed hope that it could replace pulmonary angiography because of better visualisation of the segmental and subsegmental vessels and thinner collimation. Although the overall sensitivity of MSCT was only 83% in the large Prospective Investigation on Pulmonary Embolism Diagnosis II (PIOPED II) study,3 the negative predictive value of MSCT was 95% in patients with a low clinical probability of pulmonary embolism and 89% in those with an intermediate clinical probability.
To increase the diagnostic yield, the PIOPED II study also investigated the added value of undertaking CT venography of the legs during the same procedure. Although the sensitivity of the combined examination was higher (90%) than it was with chest CT alone, the negative predictive value was only marginally increased (97% vs 95%).3 This finding is compounded by data from two large studies assessing MSCT.1, 2 In the first, which included 756 consecutive patients who were referred to the emergency department for clinically suspected pulmonary embolism,1 the proportion of patients in whom a proximal deep-venous thrombosis was detected by venous compression ultrasonography of the leg despite a negative MSCT was only three of 324 (0·9% [95% CI 0·3–2·7]). In the second study,2 the 3-month thromboembolic risk was low (1·3% [0·7–2·0]) in patients who were left untreated because of a negative chest CT, despite the fact that venous ultrasonography was not undertaken.
Collectively, these results suggest that MSCT might be safe as a stand-alone test and that the added value of venous ultrasonography is questionable. To assess this notion, we compared two strategies: clinical probability assessment and either ELISA D-dimer measurement and MSCT (DD-CT strategy) or ELISA D-dimer measurement, venous compression ultrasonography of the leg, and MSCT (DD-US-CT strategy).
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Study setting
The study was designed as a multicentre, randomised, prospective, non-inferiority trial. Data were collected from Jan 10, 2005 to Aug 30, 2006, at six participating medical centres that serve as general and teaching hospitals (Switzerland: Centre Hospitalier Universitaire Vaudois, Lausanne; Geneva University Hospital, Geneva. France: Hôpital Européen Georges-Pompidou, Paris; CHU Angers, Angers; CHU de la Cavale Blanche, Brest. Belgium: Saint Luc University Hospital, Brussels). All patients
Results
Figure 2, Figure 3 show the trial profile in the per-protocol and intention-to-diagnose populations, respectively. During the study period, 1819 patients with clinically suspected pulmonary embolism were randomly assigned: 916 in the DD-US-CT group and 903 in the DD-CT group. Six patients withdrew consent and one died before any test could be undertaken, leaving 1812 patients in the intention-to-diagnose analysis. Table 2 shows the baseline characteristics of the two groups. In the
Discussion
This randomised, multicentre, non-inferiority trial has shown that a strategy combining ELISA D-dimer measurement and MSCT was non-inferior to a similar strategy using D-dimer followed by venous compression ultrasonography of the leg and MSCT for exclusion of pulmonary embolism. The 3-month thromboembolic risk in both groups of the study was similar to that recorded in patients who were left untreated on the basis of a negative pulmonary angiography.19 The study included a large number of
References (27)
- et al.
Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism
Lancet
(1991) - et al.
Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review
Clin Radiol
(2001) - et al.
Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice computed tomography in outpatients: an outcome study
J Thromb Haemost
(2005) - 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) - et al.
Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism
J Thromb Haemost
(2008) - et al.
Diagnosis and management of subsegmental pulmonary embolism
J Thromb Haemost
(2006) - et al.
Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism
J Thromb Haemost
(2007) - et al.
Multidetector-row computed tomography in suspected pulmonary embolism
N Engl J Med
(2005) - et al.
Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography
JAMA
(2006) - et al.
Multidetector computed tomography for acute pulmonary embolism
N Engl J Med
(2006)
Central pulmonary tromboembolism: diagnosis with spiral volumetric CT with the single-breath-hols technique. Comparison with pulmonary angiography
Radiology
The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism
Arch Intern Med
Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review
Ann Intern Med
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These authors contributed equally