Our study demonstrates that the availability of baseline imaging conducted after completion of anticoagulant therapy in unprovoked DVT and/or PE patients significantly improves the ability to classify suspected recurrent VTE. As a result, when baseline imaging is available, a lower proportion of patients have an inconclusive diagnosis of recurrent VTE. Baseline imaging also improves interobserver agreement for classification of suspected recurrent VTE.
The strengths of our study include: (i) the use of actual patient data that provide a real-world combination of suspected recurrent events – that is, we included patients with all types of index event (isolated DVT, isolated PE, or DVT and PE), all patterns of residual disease on baseline imaging (isolated residual pulmonary vascular obstruction, isolated RVO, or both), and all possible types of suspected recurrent VTE (recurrent VTE presenting as isolated recurrent DVT, recurrent isolated PE, or recurrent DVT and PE); (ii) the fact all of our patient charts had index VTE imaging reports available, which is not always the case in real-world practice – despite this information, baseline imaging was of incremental benefit in classifying patients; and (iii) the randomization, which limited selection bias and provided a control group.
There are limitations to our study. First, baseline imaging was restricted to the index symptomatic VTE site. However, it is well known that 50% of patients with symptomatic DVT have associated asymptomatic perfusion defects on V/Q scan when performed. Similarly, asymptomatic DVT is found in nearly 50% of patients with acute PE . Therefore, we probably underestimated the proportion of residual obstruction in the pulmonary and lower extremity vasculature, and hence a larger proportion of patients would have had documented residual disease, which may have to have led to an overestimation of recurrent disease in our study patients. Second, this was a retrospective comparison analysis, and the results may not be applicable to daily clinical practice, because physicians may have altered their diagnostic pursuit when faced with the uncertainty of classification that we have documented in this study. Nonetheless, when clinicians are confronted with this common clinical scenario, comparison with index or baseline imaging results is always retrospective in nature, and suspected recurrent VTE imaging results are often also retrospectively reviewed by other healthcare clinicians who are subsequently involved in a patient’s care. Third, only patients with a first unprovoked VTE were included in our study. Therefore, our results do not apply to patients with prior multiple recurrent VTEs or provoked VTE. Nonetheless, recurrent VTE in patients with multiple prior VTEs is more likely to be non-classifiable, given the higher likelihood of residual vascular obstruction. Fourth, although D-dimer results were made available to adjudicators in both groups if they were available, they were not systematically collected for all patients at the time of suspected recurrent VTE. If D-dimer results had been available for all patients, this may have improved overall classifiability and perhaps altered our study results. However, although evidence suggests that a negative D-dimer result safely rules out VTE in patients with a prior VTE, the clinical utility of the test is halved in this group: in a post hoc analysis of a diagnostic management outcome study, only 15.9% of patients with a previous history of VTE had PE ruled out on the basis of the combination of a non-high clinical probabillity of PE and a negative D-dimer result, as compared with 32.7% of patients with no previous episode . Finally, whether baseline imaging is cost-effective or not deserves further attention. However, given that 50% of patients present with suspected recurrent VTE during the first 2 years after anticoagulant therapy discontinuation , it would be useful in a large proportion of patients after completion of therapy for a first unprovoked VTE, and as such, in our view, is likely to be cost-effective when one considers the costs and consequences of subsequent misdiagnosis, including lifelong anticoagulation in false-positives.
In conclusion, conducting baseline imaging after completion of anticoagulant therapy should be strongly considered; baseline imaging appears to increase diagnostic certainty in the common group of patients with unprovoked VTE who subsequently present with suspected recurrent VTE, and therefore probably provides a more solid basis on which to make a decision to indefinitely resume lifelong anticoagulation.