Should lifelong anticoagulation for unprovoked venous thromboembolism be revisited?

Abstract

Venous thromboembolism [VTE] is a common medical condition that has significant morbidity and mortality. Although stringent guidelines recommend lifelong anticoagulation for patients with unprovoked VTE, the optimal management strategy for their long term treatment remains controversial. Whereas in cancer-associated VTE and second unprovoked VTE lifelong anticoagulation is universally accepted, a careful analysis of the benefit vs. risk of long-term anticoagulation following a first unprovoked VTE should be considered as case fatality rates [CFR] from VTE appear more pronounced in the first few months. The CFR from major bleeding remains constant throughout therapy. Therefore, the risk of bleeding may be underestimated over longer treatment periods relative to the morbidity of recurrent VTE which appears to peak in the first year. The current review highlights the balance between the recurrence risk and bleeding risks in the era of direct oral anticoagulants. Vitamin K antagonists have been the standard of care for over 50 years bearing significant bleeding risks. The new oral anticoagulants [NOACs] have shown similar efficacy and perhaps a questionable improved safety profile when compared to warfarin. Aspirin has historically not been a useful agent in the management of VTE. However, two recent trials [WARFASA and ASPIRE] showed a likely 20-30 % risk reduction when compared to placebo for recurrent VTE after initial anticoagulation. The risk of major hemorrhage was low in both trials. With the emergence of NOACs and the increased utility of aspirin, there are multiple therapeutic options for long term management for VTE. Given comparable efficacy and improved safety of NOACs and aspirin, the risk benefit of anticoagulation is improving. A risk stratification model may help identifying patients at high risk for recurrence necessitating a lifelong anticoagulation. This cohort should be separated from a low risk group that may benefit from clinical observation, aspirin or NOACs. Prospective clinical trials are needed to support these clinical observations.

Keywords: DVT; Duration; NOACs; PE; Recurrence; Venous thromboemobolism; Warfarin.

Fig. 1

Recurrence of DVT and PE over time after an unprovoked episode compared to the risks of major bleeding with anticoagulation using warfarin or rivaroxaban (modified from Martinez et al., 2014 [19])