New oral anticoagulants in the treatment of DVT and PE

This editorial contains a rundown of the phase III trials for all four agents that have been studied. It is available as free full text. Key points:

...First, all DOACs were shown consistently to be non-inferior compared with well-managed warfarin. The high quality of warfarin management, with a superior time in international normalized ratio target range compared with daily clinical practice, strengthens both the internal and external validity of these studies but also underscores that well-managed warfarin is an effective therapy for preventing recurrent VTE...

To me the time in therapeutic range for warfarin was not that great in those trials. However, you can be sure it was better than it is in the community.

Second, all DOACs caused less bleeding. Importantly, the shift in the bleeding pattern that is observed in patients with atrial fibrillation, with less intracranial, less life-threatening, and less critical site bleedings, is also seen in patients with VTE. DOACs cause less major (Table) and less intracranial bleedings in patients with VTE, but caution remains, in particular for patients at risk for gastrointestinal bleeding.

Third, the new regimens differ in their initial treatment approach. The first couple of weeks are of particular interest because of the high risk for recurrence and bleeding. The dual-drug bridging period with overlapping heparin and vitamin K antagonists constitutes a risk for overtreatment and undertreatment and requires intensive international normalized ratio monitoring that is labor- and time-consuming and costly. Furthermore, lessons have been drawn from the observation that ximelagatran9 and idraparinux,10 administered without heparin lead-in and without initial intensified dosing, caused more early recurrence compared with heparin/vitamin K antagonists. This helps to explain the 2 different strategies of DOACs for acute VTE (ie, including a heparin lead-in or starting with an intensified dose)...

Parenteral heparin will remain a preferred treatment option for many patients, especially those with more severe clinical presentations and patients with high thrombus burden who are admitted to the hospital. When parenteral heparin has been administered for 5 to 10 days, peroral anticoagulation with dabigatran or edoxaban can be continued.

For most cancer patients, the continued treatment with LMWH is currently the recommended and preferred therapy. Patients with active cancer for whom long-term treatment with LMWH was anticipated were not eligible for the phase III trials. Hence, additional studies are needed in cancer patients with continued LMWH and not warfarin as the comparator before DOACs can be considered an alternative standard to continued LMWH in these patients...

Besides particular patient characteristics, also less common clinical manifestations of VTE require our attention. DOACs have only been studied in patients with proximal DVT of the lower limb or hemodynamically stable pulmonary embolism. Patients with distal DVT, DVT of the upper limb, superficial thrombophletitis, or catheter-related thrombosis, patients who underwent thrombolysis, and patients with cerebral vein or mesenteric vein thrombosis have not been studied yet.