Diagnosing pulmonary embolism in the context of common alternative diagnoses in primary care

Rationale: Clinical decision rules and D-dimer testing are available for general practitioners to distinguish pulmonary embolism (PE) from common alternative cardiopulmonary diagnoses in patients with a suspicion of PE. However, D-dimer testing is often falsely elevated, leading to unneeded, costly and potential harmful referrals for CT pulmonary angiography (CTPA). To alleviate this problem, a risk-tailored diagnostic approach was recently tested and validated with good results in secondary care: the YEARS-strategy. In secondary care, this algorithm leads to an absolute reduction of 14% of CTPAs with a completely similar safety (only 0.4% missed PE cases), as compared to a fixed D-dimer threshold of 500 mcg/L. This strategy however is not yet implemented in primary care, and awaits validation in this healthcare setting.

Objective: Our primary objective is to prospectively implement and validate the YEARS strategy in primary care. Secondary objectives are, (i) to quantify the added diagnostic value of C-reactive protein (CRP) to a clinical assessment and D-dimer testing in order to enhance distinguishing PE from a pneumonia, (ii) to develop a polytomous logistic model for estimating the diagnostic probability of both PE and pneumonia, and (iii) to statistically quantify predictors for assessing PE as most likely diagnosis by GPs.

Study design: prospective diagnostic cohort study.

Study population: this study will include 750 patients with subacute new onset or worsening of existing shortness of breath with or without chest symptoms, which makes them suspected of having PE.

Intervention: participants will be managed by their GP according to the YEARS-strategy. Furthermore, additional blood will be drawn for CRP. There will be a clinical follow-up in primary care for 3 months in all patients to establish the final diagnosis.

The primary hypothesis is that a novel clinical decision rule for pulmonary embolism (the YEARS strategy) is at least as safe as previous studies, yet with an increased proportion of patients safely not referred for CTPA, thus fewer false-positive D-dimer tests

There will be a clinical follow-up in primary care for 3 months in all patients to establish the final diagnosis.

The intervention is a novel clinical decision rule for patients with a suspected pulmonary embolism: the YEARS-strategy. In this strategy, the physician scores three clinical items: (i) haemoptysis, (ii) clinical signs suggestive of deep venous thrombosis, and (iii) PE considered the most likely diagnosis. If none of these items is present, a D-dimer threshold of 1000 mcg/L is applied, while if one or more items are present, the classical threshold of 500 mcg/L is used. If a suspected patient has a D-dimer below either threshold, PE is safely ruled out. Furthermore, additional blood will be drawn for CRP in order to quantify the added diagnostic value of CRP in the diagnostic management of PE.