Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysisBMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4363 (Published 24 July 2019) Cite this as: BMJ 2019;366:l4363
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Long term risk of fatal pulmonary embolism after discontinuation of anticoagulant treatment for unprovoked venous thromboembolism
With great interest I read the relevant and well performed systematic review and meta-analysis on the long term risk of symptomatic recurrent venous thromboembolism (VTE) after discontinuation of anticoagulant treatment by Khan and colleagues (Khan F, et al. BMJ 2016; 366: doi:https://doi.org/10.1136/bmj.l4363). They provide incidence estimates that are important to daily clinical practice and underline current guideline recommendations to consider indefinite anticoagulation in patients with unprovoked PE without a high risk of anticoagulant-associated major bleeding because of the considerable 10-year cumulative incidence with the upper limit of the 95% confidence interval as high as 45%.
One of the strengths of this study is the application of the International Society on Thrombosis and Haemostasis (ISTH) definition of unprovoked PE (Kearon C, et al. J Thromb Haemost 2016;14:1480-3) in the study selection criteria. Very recently, the ISTH also proposed a standardized definition of pulmonary embolism (PE) related death. Considering the very different definition of fatal PE among the included studies in this meta-analysis (van der Wall SJ et al, Eur Respir Rev 2018;27:180094; Kraaijpoel N, et al, J Thromb Haemost 2019; doi: 10.1111/jth.14570), it would be greatly appreciated if the authors could report the rate of fatal recurrent VTE and associated case-fatality rate according to this new definition as well. This would lead to a better understanding of the impact of recurrent VTE in patients with a first unprovoked VTE event who stop anticoagulant treatment.
The authors report the incidence of VTE recurrences per time interval after anticoagulant discontinuation, for both sexes and for the different initial presentations of VTE. The incidence of fatal recurrent VTE however, is only reported per time interval. It would be very interesting to also know these rates of fatal recurrent VTE for the different initial presentations of VTE, i.e. limited to proximal deep vein thrombosis (DVT) or involving acute PE as well. It is often hypothesized that the risk of a fatal recurrence after DVT is lower than after PE, since DVTs tend to recur as DVT and PEs as PE, with PE being the lethal clinical presentation of VTE. Notably, a recent meta-analysis on the same topic but with less detailed data, could not demonstrate a higher incidence of fatal recurrent VTE after an index PE than after an index DVT (van der Wall SJ et al, Eur Respir Rev 2018;27:180094). Would the authors be able to report the rate of fatal recurrent VTE after initial DVT and after initial PE seperately to shed more light on this issue?
Competing interests: No competing interests