Elsevier

The Lancet

Volume 390, Issue 10091, 15–21 July 2017, Pages 289-297
The Lancet

Articles
Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study

https://doi.org/10.1016/S0140-6736(17)30885-1Get rights and content

Summary

Background

Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism.

Methods

We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193.

Findings

3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36–0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07–0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12–16).

Interpretation

In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups.

Funding

This study was supported by unrestricted grants from the participating hospitals.

Introduction

The clinical diagnosis of pulmonary embolism is non-specific and should therefore be followed by objective testing. Because of its diagnostic accuracy and wide availability, multidetector row computed tomography pulmonary angiography (CTPA) is the imaging test of choice to confirm acute pulmonary embolism in most patients. Increasing use of CTPA with diminishing prevalence of pulmonary embolism—to even less than 10%1—has led to overdiagnosis of mostly subsegmental pulmonary embolism and unnecessary risks of radiation exposure and contrast medium induced nephropathy.2, 3, 4, 5, 6 To avoid these problems, validated diagnostic algorithms for suspected acute pulmonary embolism, using sequential testing, have been introduced.7 In these algorithms, a normal D-dimer test result in patients with low probability safely excludes pulmonary embolism.8 Correct application of these algorithms obviates the need for CTPA in 20–30% of patients, with an overall 3-month diagnostic failure rate of less than 1·5% after initial negative ruling of the algorithm.7, 8, 9 An age-adjusted D-dimer threshold (age × 10 ng/mL for patients aged >50 years) has been validated prospectively, reporting an absolute reduction of 11·6% (95% CI 10·5–12·9) in the need for CTPA.10 Importantly, only patients aged 50 years or older, and foremost those older than 75 years benefit from this strategy whereas when considering the life-time attributable cancer risk, the exposure to unnecessary radiation is considered more relevant to younger individuals, particularly women.3

Research in context

Evidence before this study

We did not do a systematic search on this topic. However, on the basis of several prospective management studies, patients with clinically suspected pulmonary embolism should be managed according to a validated diagnostic algorithm consisting of clinical decision rule such as the Wells' rule, which predicts the pretest probability of pulmonary embolism, a D-dimer test, and eventually a multirow detector computed tomography pulmonary angiography (CTPA). By using such a diagnostic algorithm, pulmonary embolism can be excluded without CTPA in 20–30% of patients, thereby omitting radiation exposure. In a meta-analysis, the 3-month risk of venous thromboembolism in patients managed without CTPA is 0·65% (95% CI 0·38–1·11). Importantly, most CTPA results are still negative for pulmonary embolism, indicating that many patients are exposed to unnecessary radiation. An age-adjusted D-dimer threshold (age × 10 ng/mL for patients >50 years) has been validated prospectively, reporting an absolute reduction of 11·6% (95% CI 10·5–12·9) in the need for CTPA. Only patients aged 50 years or older, and foremost those older than 75 years benefit from this strategy whereas the exposure to unnecessary radiation might be more relevant to younger individuals, particularly women. Therefore, one of the remaining challenges is to further reduce the number of CTPA without reducing the safety of diagnostic management.

Additionally, despite firm evidence of its safety and efficiency, several studies reported that adherence to recommended diagnostic algorithms outside clinical studies is poor. This finding might be partly due to its complexity, and insufficient time at busy emergency departments, which hampers the use of sequential tests. Improved adherence to the algorithm has been shown to significantly decrease the mean number of diagnostic tests used along with—and more importantly—the number of diagnostic failures. For instance, one study reported a failure rate of 7·7% in patients who were managed inappropriately compared with only 1·2% in patients managed appropriately.

Added value of this study

In this study, a novel and simplified diagnostic algorithm for suspected acute pulmonary embolism (the YEARS algorithm) has been prospectively investigated. The YEARS algorithm consists of only three items of the original Wells' clinical decision rule—ie, clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis—were found to be the most predictive for pulmonary embolism. This simplified clinical decision rule was combined with variable D-dimer threshold depending on the presence of one of these items. In patients in whom none of the items were present, a D-dimer test threshold of 1000 ng/mL was used whereas a D-dimer threshold of 500 ng/mL was used when one or more items were present.

Our study showed that the YEARS algorithm is safe during 3 months of follow-up in all patients who had pulmonary embolism excluded. In patients managed without CTPA, the 3-month risk of venous thromboembolism was well comparable to the risk reported by a meta-analysis after the current standard algorithm was used. The advantage of the YEARS algorithm is an absolute reduction of 14% of CTPA compared with the current standard algorithm and, importantly, an 8·7% reduction compared with the age-adjusted D-dimer threshold. In this context, patients younger than 50 years also benefit from the YEARS algorithm.

Implications of all the available evidence

There are two main advantages of the YEARS algorithm. First, the YEARS algorithm leads to an absolute 14% decrease in the number of CTPA examinations that is applicable to all ages. This decrease is a major step forward in reducing unnecessary radiation exposure in patients with suspected pulmonary embolism. Second, the YEARS algorithm leads to a simpler and more efficient diagnostic management of patients with suspected pulmonary embolism than standard diagnostic algorithms such as the Christopher Study algorithm, which is likely to improve the adherence to correct diagnostic management of suspected pulmonary embolism and thereby lead to better safety and efficiency in daily clinical practice.

Despite firm evidence of its safety and efficiency, adherence to recommended diagnostic strategies in clinical practice is variable. This variation might be partly due to complexity of these strategies, and insufficient time at busy emergency departments, which hampers the use of sequential tests.11, 12, 13, 14 In daily practice, D-dimer testing is frequently ordered and known at a low clinical threshold or even before the clinical assessment.15, 16 Improved adherence to the algorithm, for instance by implementation of a clinical decision support system, has been shown to significantly decrease the mean number of diagnostic tests used along with—and more importantly—the number of diagnostic failures.17, 18

On the basis of a post-hoc derivation and validation study,19 three items of the original Wells' clinical decision rule—ie, clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis—were the most predictive for pulmonary embolism. They allowed the use of a differential D-dimer threshold based on the presence of one of these items, without losing sensitivity. Hence, this algorithm—which we call YEARS—involves the simultaneous assessment of only the three abovementioned items and a D-dimer test threshold of 500 ng/mL in presence, and 1000 ng/mL in absence of one of the YEARS items. The YEARS algorithm was designed to be more easily applied in a busy clinical practice than currently used diagnostic strategies, and to further decrease the number of necessary CTPA examinations in patients of all ages. In this study, we aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism.

Section snippets

Study design and patients

We did a prospective, multicentre, cohort outcome study evaluating the safety and efficiency of the YEARS algorithm in patients with suspected acute pulmonary embolism between Oct 5, 2013, and July 9, 2015 (figure 1).19 The algorithm was implemented as standard diagnostic strategy in 12 participating hospitals in the Netherlands. The full study protocol is available in the appendix.

Consecutive outpatients and inpatients with clinically suspected acute (first or recurrent) pulmonary embolism

Results

From Oct 5, 2013, to July 9, 2015, 3616 consecutive patients with clinically suspected pulmonary embolism were screened in the 12 participating hospitals, of whom 151 (4·2%) were excluded (figure 2). Table 1 summarises the baseline characteristics. Overall, pulmonary embolism was detected in 456 (13%) of 3465 patients: in 55 (3·2%) of 1743 patients with none of the YEARS items and 401 (23%) of 1722 patients with one or more YEARS items.

According to the intention-to-diagnose approach, of the

Discussion

Our study showed that the YEARS algorithm safely excluded acute pulmonary embolism. An absolute 14% decrease in the need for CTPA was achieved, compared with the standard algorithm. The 3-month incidence of venous thromboembolism in patients who did not undergo CTPA was in line with that observed in studies using algorithms with sequential diagnostic testing and traditional two-level Wells' score, and a fixed cutoff concentration of D-dimer of 500 ng/mL: 0·43% (95% CI 0·17–0·88) in our study

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    YEARS study group is listed at the end of this paper

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