The PIOPED II trial: CT sensitive and specific for pulmonary embolism [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. Multidetector computed tomographic angiography (CTA) was highly sensitive and specific for the diagnosis of pulmonary embolism (PE) when compared to a composite reference standard.

2. When combined with computed tomographic venography (CTV), sensitivity was increased without a significant increase in the specificity, positive predictive value, or negative predictive value.

Original Date of Publication: June 2006

Study Rundown: PE refers to the blockage of one or more arteries within the lung by a blood clot or other substance that originated within another part of the body. It is a commonly considered diagnosis among patients presenting to the emergency department with shortness of breath and chest pain, and failure to diagnose PE is associated with significant mortality. Historically, the diagnosis was made by the introduction of contrast material directly into the pulmonary arteries by a catheter. This technique was replaced by ventilation-perfusion (VQ) scanning, which compares patterns of blood flow and oxygenation in the lung using a radioactive tracer. Though significantly less invasive, VQ scanning was often difficult to interpret and was itself replaced by CTA beginning in the 1980s and 1990s. Early reports of the diagnostic performance of CTA were generally positive but mixed, and the optimal method for evaluating patients with suspected PE initially remained uncertain. In the second Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) trial, CTA with and without concomitant lower extremity CTV was compared with a composite reference standard including both VQ scanning and conventional angiography. The results of this trial showed that both CTA and combined CTA-CTV were highly sensitive and specific for the diagnosis of PE, and that the combination of clinical judgment with the results from CTA or CTA-CTV evaluation was sufficient to accurately rule-in and rule-out PE in the vast majority of patients.

Click to read the study in NEJM

In-Depth [prospective cohort]: This prospective trial was conducted at 8 clinic sites throughout North America. All adult patients with signs and symptoms concerning for acute PE who were referred for evaluation were consecutively screened for enrollment (n=7284). Both inpatients and outpatients were considered. Key exclusion criteria included anticoagulant use, hemodialysis, critical illness, patients on ventilators, and recent myocardial infarction. Following screening and consent, all enrolled patients (n=1090) underwent combined CTA-CTV, as well as one or more of the components that together formed the composite reference standard. This included VQ scanning, lower extremity venous ultrasonography with Doppler imaging, and, when necessary, digital subtraction angiography (DSA) of the pulmonary arteries.  All imaging studies were reviewed by 2 blinded radiologists unaffiliated with the clinical sites, with additional radiologists serving as arbiters in the event of discordant interpretations. Patients were considered to have a positive CTA if there was any partial or complete filling defect identified within one or more pulmonary arteries, and a positive CTV if there was any partial or complete filling defect identified within one of the lower extremity veins. Using the composite reference standard, patients were diagnosed with PE if any of the following conditions were met: high probability VQ scan in a patient without a history of PE; filling defect on pulmonary DSA; or visualized lower extremity clot by ultrasound. A total of 824 patients (mean age 51.7±17.1 years; 62% women; 89% outpatient) successfully completed both CTA-CTV and the composite reference standard. Among this cohort, 192 PEs were diagnosed. For those with diagnostic-quality CTA alone (773 patients, 94%), the sensitivity was 83% and the specificity was 96%, while the positive and negative predictive values were 86% and 95%, respectively. Considering those patients with diagnostic-quality combined CTA-CTV (737 patients, 89%) separately, the sensitivity was 90% and the specificity was 95%, while the positive and negative predictive values were 85% and 97%, respectively. The results varied substantially by clinical suspicion, with a positive predictive value of 96% among those with a high pre-test probability of PE and a positive predictive value of 58% among those with a low-pretest probability. Complications associated with CTA-CTV were rare and included mild allergic reactions and transiently increased creatinine.

Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, et al. Multidetector Computed Tomography for Acute Pulmonary Embolism. The New England Journal of Medicine. 2006 Jun 1;354(22):2317–27.

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