The original and simplified Wells rules and age-adjusted D-dimer testing to rule out pulmonary embolism: an individual patient data meta-analysis.

Essentials Evidence for the simplified Wells rule in ruling out acute pulmonary embolism (PE) is scarce. This was a post-hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The simplified Wells rule combined with age-adjusted D-dimer testing may safely rule out PE. Given its ease of use, the simplified Wells rule is to be preferred over the original Wells rule. SUMMARY: Background The Wells score and D-dimer testing can safely rule out pulmonary embolism (PE). A simplification of the Wells score has been proposed to improve clinical applicability, but evidence on its performance is scarce. Objectives To compare the performances of the original and simplified Wells scores alone and in combination with age-adjusted D-dimer testing. Methods Individual patient data from 7268 patients with suspected PE enrolled in six management studies were used to evaluate the discriminatory performances of the original and simplified Wells scores. The efficiency and failure rate of the dichotomized original and simplified scores combined with age-adjusted D-dimer testing were compared by use of a one-stage random effects meta-analysis. Efficiency was defined as the proportion of patients in whom PE could be considered to be excluded on the basis of a 'PE unlikely' Wells score and a negative age-adjusted D-dimer test result. Failure rate was defined as the proportion of patients with symptomatic venous thromboembolism during a 3-month follow-up. Results The discriminatory performances of the original and simplified Wells scores were comparable (c-statistic 0.73 [95% confidence interval (CI) 0.72-0.75] versus 0.72 [95% CI 0.70-0.73]). When combined with age-adjusted D-dimer testing, the original and simplified Wells rules had comparable efficiency (3% [95% CI 25-42%] versus 30% [95% CI 21-40%]) and failure rates (0.9% [95% CI 0.6-1.5%] versus 0.8% [95% CI 0.5-1.3%]). Conclusion The original and simplified Wells rules combined with age-adjusted D-dimer testing have similar performances in ruling out PE. Given its ease of use in clinical practice, the simplified Wells rule is to be preferred.

PO-07 - Excluding pulmonary embolism in cancer patients using the Wells rule and age-adjusted D-dimer testing: an individual patient data meta-analysis.

INTRODUCTION: Among patients with clinically suspected pulmonary embolism (PE), imaging and anticoagulant treatment can be safely withheld in approximately one-third of patients based on the combination of a "PE unlikely" Wells score and a D-dimer below the age-adjusted threshold. The clinical utility of this diagnostic approach in cancer patients is less clear. AIM: To evaluate the efficiency and failure rate of the original and simplified Wells rules in combination with age-adjusted D-dimer testing in patients with active cancer. MATERIALS AND METHODS: Individual patient data were used from 6 large prospective studies in which the diagnostic management of PE was guided by the original Wells rule and D-dimer testing. Study physicians classified patients as having active cancer if they had new, recurrent, or progressive cancer (excluding basal-cell or squamous-cell skin carcinoma), or cancer requiring treatment in the last 6 months. We evaluated the dichotomous Wells rule and its simplified version (Table). The efficiency of the algorithm was defined as the proportion of patients with a "PE unlikely" Wells score and a negative age-adjusted D-dimer, defined by a D-dimer below the threshold of a patient's age times 10 µg/L in patients aged ≥51 years. A diagnostic failure was defined as a patient with a "PE unlikely" Wells score and negative age-adjusted D-dimer who had symptomatic venous thromboembolism during 3 months follow-up. A one-stage random effects meta-analysis was performed to estimate the efficiency and failure. RESULTS: The dataset comprised 938 patients with active cancer with a mean age of 63 years. The most frequent cancer types were breast (13%), gastrointestinal tract (11%), and lung (8%). The type of cancer was not specified in 42%. The pooled PE prevalence was 29% (95% CI 25-32). PE could be excluded in 122 patients based on a "PE unlikely" Wells score and a negative age-adjusted D-dimer (efficiency 13%; 95% CI 11-15). Two of 122 patients were diagnosed with non-fatal symptomatic venous thromboembolism during follow-up (failure rate 1.5%; 95% CI 0.13-14.8). The simplified Wells score in combination with a negative age-adjusted D-dimer had an efficiency of 3.9% (95% CI 2.0-7.6) and a failure rate of 2.4% (95% CI 0.3-15). CONCLUSIONS: Among cancer patients with clinically suspected PE, imaging and anticoagulant treatment can be withheld in 1 out of every 8 patients by the original Wells rule and age-adjusted D-dimer testing. The simplified Wells rule was neither efficient nor safe in this population.

A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism.

BACKGROUND: An 'unlikely' clinical decision rule with a negative D-dimer result safely excludes pulmonary embolism (PE) in 30% of presenting patients. We aimed to simplify this diagnostic approach and to increase its efficiency. METHODS: Data for 723 consecutive patients with suspected PE were analyzed (prevalence of PE, 22%). After constructing a logistic regression model with the D-dimer test result and items from the Wells' score, we identified the most prevalent combinations of influential items and selected new D-dimer positivity thresholds. The performance was separately validated with data from 2785 consecutive patients with suspected PE. RESULTS: Three Wells items significantly added incremental value to the D-dimer test: hemoptysis, signs of deep vein thrombosis and 'PE most likely'. Based on the most frequent combinations of these three items, we identified two groups: (i) none of these three items positive (41%); (ii) one or more of these items positive (59%). When applying a 1000 µg/L D-dimer threshold in group 1 and 500 µg/L in group 2, PE could be excluded without CT scanning in 36%, at a false-negative rate of 1.2% (95%, 0.04-3.3%). In the validation set, these proportions were 46% and 1.9% (95% CI, 1.2-2.7%), respectively. Using the conventional Wells score with a normal D-dimer result, these rates were, respectively, 22% and 0.6% (95% CI, 0.10-2.4%). CONCLUSION: Combining Wells items with the D-dimer test resulted in a simplified decision rule, which reduces the need for CT scanning in patients with suspected PE. A prospective validation is required before it can be implemented in clinical practice.

Variable D-dimer thresholds for diagnosis of clinically suspected acute pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is frequently requested using diagnostic algorithms for suspected pulmonary embolism (PE). For suspected deep vein thrombosis, it was recently shown that doubling the D-dimer threshold in patients with low pretest probability safely decreased the number of ultrasonograms. We evaluated the safety and efficiency of a similar strategy in patients with suspected PE. METHODS: We performed a post-hoc analysis of 2213 consecutive patients of two cohort studies with suspected PE who were managed according to current standards: PE ruled out in case of unlikely probability (Wells rule ≤ 4 points) and a D-dimer level < 0.5 µg mL(-1) . CTPA was performed in all other cases. All patients were followed for 3 months. We calculated 3-month venous thromboembolism (VTE) incidence and the number of required CTPAs for selective D-dimer thresholds in patients with low clinical probability (< 2 points, D-dimer threshold < 1.0 µg mL(-1) ) and intermediate probability (2-6 points, D-dimer threshold < 0.5 µg mL(-1) ). RESULTS: Using standard management, PE could be excluded without CTPA in 26% of patients, with a 3-month VTE incidence of 0.88% (95% confidence interval [CI] 0.29-2.1%). Using selective D-dimer thresholds, PE could be excluded without CTPA in 36% of patients, with a 3-month VTE incidence of 2.1% (95% CI 1.2-3.4%) in patients managed without CTPA, an increase of 1.2 percentage points (95% CI -0.3 to 2.2). CONCLUSIONS: Applying selective D-dimer thresholds reduces the need for CTPA by 11 percentage points but is associated with an increased failure rate. Prospective studies should evaluate the safety and net clinical benefit of this approach.

Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study.

BACKGROUND: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non-randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. OBJECTIVE: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. PATIENTS AND METHODS: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow-up. RESULTS: Of 297 included patients, who all completed the follow-up, six (2.0%; 95% confidence interval [CI] 0.8-4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3 months of follow-up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08-2.4). CONCLUSION: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).

Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis.

INTRODUCTION: The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an "unlikely" CDR (

Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis.

INTRODUCTION: Several outcome studies have ruled out acute pulmonary embolism (PE) by normal computed tomography pulmonary angiography (CTPA). We performed a meta-analysis in order to determine the safety of this strategy in a specific group of patients with a strict indication for CTPA, that is, 'likely' or 'high' clinical probability for PE, an elevated D-dimer concentration, or both. METHODS: Studies that ruled out PE by normal CTPA, with or without subsequent normal bilateral compression ultrasonography (CUS), in patients with a strict indication for CTPA, were searched for in Medline, EMBASE, Web of Science and the Cochrane dataset. The primary endpoint was the occurrence of (fatal) venous thromboembolism (VTE) in a 3-month follow-up period. RESULTS: Three studies were identified that excluded PE by CTPA alone (2020 patients), and three studies that performed additional CUS of the legs after normal CTPA (1069 patients). The pooled incidence of VTE at 3 months was 1.2% [95% confidence interval (CI) 0.8-1.8] based on a normal CTPA result as a sole test, and 1.1% (95% CI 0.6-2.0) based on normal CTPA and negative CUS findings, resulting in negative predictive values of 98.8% (95% CI 98.2-99.2) and 98.9% (95% CI 98.0-99.4), respectively. This compares favorably with the VTE failure rate after normal pulmonary angiography (1.7%, 95% CI 1.0-2.7). The risk of fatal PE did not differ between the diagnostic strategies (0.6% vs. 0.5%). CONCLUSION: A normal CTPA result alone can safely exclude PE in all patients in whom CTPA is required to rule out this disease. There is no need for additional ultrasonography to rule out VTE in these patients.