Anticoagulant therapy is effective for the treatment of acute venous thromboembolism (VTE): deep vein thrombosis (DVT) and pulmonary embolism (PE) [
1]. For more than half a century, standard anticoagulant therapy with heparin (mainly subcutaneous low molecular weight heparin; LMWH) overlapped and followed by oral vitamin K antagonists (VKAs), such as warfarin, represented the mainstay recommended by guidelines worldwide [
2]. The combination of LMWH/VKAs given for ≥3 months is capable of significantly reducing morbidity and mortality, preventing recurrent thromboembolism (RTE) during the acute phase and avoiding long-term complications such as post-thrombotic syndrome (PTS) and secondary pulmonary hypertension (SPH) after PE [
3]. However, one of the major limitations of oral VKAs is the need for laboratory monitoring by prothrombin time test expressed as the international normalized ratio (PT-INR). In fact, this parameter must be kept in a “therapeutic range” of 2 to 3 (target 2.5) throughout the entire course of therapy (that is, time in therapeutic range; TTR), and this goal is achieved by dose adjustments. Unfortunately, it is not always possible to obtain optimal values of PT-INR due to several variables that may interfere with VKAs, such as concomitant medications and some foods, making the anticoagulant effect unstable and therefore increasing the risk of failure.
Recently, novel drugs termed “direct oral anticoagulants” (DOACs) have been introduced in clinical practice, including dabigatran, rivaroxaban, apixaban, and edoxaban, that were shown to be effective for the treatment of VTE [
4‐
7], and represented an alternative to VKAs (defined as “indirect oral anticoagulants” [
8]). DOACs have demonstrated the same efficacy and safety as standard therapy with combined LMWH/warfarin, but with the advantage of not requiring any laboratory monitoring with dose adjustments, due to a stable anticoagulant effect. In particular, in two clinical studies conducted in the setting of VTE (proximal DVT and PE) [
5,
6], the efficacy of rivaroxaban was shown to be not inferior to that of conventional anticoagulant therapy. In a pooled analysis of the two studies, the drug also yielded a similar incidence of the main safety outcome but a significant reduction in the incidence of major bleeding: hazard ratio 0.54; 95 % confidence interval (CI) 0.37 to 0.79;
p = 0.002 [
9]. In randomized clinical trials, rivaroxaban was used for the initial treatment of an acute thrombotic event with a high dose (15 mg twice daily) administered for 3 weeks followed by a standard monodose (20 mg once daily) without the support of LMWH [
5,
6]. Yet, in the real-life setting of DVT, no information is available on the switch to rivaroxaban after clinical failure with warfarin.