The quality of evidence is downgraded by indirectness (no direct comparisons between diagnostic strategies within the included studies).
A patient-level meta-analysis 1 from 4 prospective diagnostic management studies with a total of 6 148 subjects with an overall pulmonary embolism (PE) prevalence of 24% was conducted. The studies sequentially applied the Wells rule, D-dimer tests and computed tomography pulmonary angiography (CTPA) to consecutive patients with clinically suspected acute PE. The 3-month venous thromboembolism (VTE) incidence in all 4 421 patients in whom PE was excluded with a normal CTPA at baseline was 1.2% (95% CI 0.48-2.6) and the risk of fatal PE was 0.11% (95% CI 0.02-0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0% (95% CI 1.0-4.1%) and 0.48% (95% CI 0.20-1.1%) after a normal CTPA. The 3-month incidence of VTE was 6.3% (95% CI 3.0-12) in patients with a Wells rule >6 points.
A systematic review 2 included 6 studies with a total of 6 947 subjects; 3 studies were identified that excluded PE by CTPA alone and 3 studies that performed additional compression ultrasonography (CUS) of the legs after normal CTPA. Patients had a strict indication for CTPA, that is, a clinical decision rule indicating 'likely' or 'high' clinical probability for PE, an elevated D-dimer concentration, or both. Duration of follow-up was three months in all studies. The overall proportionof inconclusive CT scan results was 1.8% (range 0.9% to 4.6%). The overall incidence of PE by positiveCTPA in these cohorts was 28% (range 18% to 36%).
CTPA alone: Of all 2 020 patients with an initial normal CTPA result, 25 (1.2%, 95% CI 0.80 to 1.8) were diagnosed with venous thromboembolism (VTE) in a 3-month follow-up period. Of these, 12 (12/2 020; 0.60%, 95% CI 0.40 to 1.1) were classified as fatal PE. The negative predictive value (NPV) for symptomatic VTE in 3 months following a normal CTPA result was 98.8% (95% CI 98.2 to 99.2). The pooledsensitivity for detecting PE by CTPA alone was 97.3% (95% CI 96.1 to 98.2). CUS of the legs subsequent to a normal CTPA: 1 069 patients with a normal CTPA result were identified; 21 cases of DVT (21/1 069; 2.4%, 95% CI 1.6 to 3.7) were identified by CUS performed shortly after the CTPA. During 3 months of followup, 9 additional patients (9/1048; 1.1%, 95% CI 0.60 to 2.0) with an initially normal CTPA result and a normal CUS result were diagnosed with symptomatic VTE. Four of these 1048 patients in whom VTE was excluded, and who were not treated with anticoagulants, died (4/1048; 0.50%, 95% CI 0.20 to 1.1), possibly as a consequence of PE. The NPV for symptomatic VTE in 3 months after a normal CTPA result followed by CUS was 98.9% (95% CI 98.0 to 99.4). The sensitivity for detecting PE by CTPA combined with CUS was 97.4% (95% CI 95.1 to 98.6).
The NPV of CTPA alone compares favorably with the VTE failure rate (1.7%, 95% CI 1.0 to 2.7) after a normal invasive pulmonary angiography and also the mortality rate observed after normal CTPA is quite similar with the 3-month PE-associated mortality rate (0.3%, 95% CI 0.02 to 0.7) after a normal invasive pulmonary angiography 3.
Clinical comments:The accuracy of CTPA is dependent on the technical features of the device. The conclusion may be only applicable to multidetector devices. Only outpatients were included in the included studies, and some uncertainty remains whether the results can be applied to (in)patients with a high pre-test probability of PE.
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