"New therapies in everyday clinical practice" was the title of a session at the DGIM Congress at which Prof. Dr. Edelgard Lindhoff-Last, Frankfurt/Main, spoke. Her topic: Direct oral anticoagulants (DOACs) in oncology and in everyday clinical practice.
The renowned expert in angiology and haemostaseology, Prof. Dr. Edelgard Lindhoff-Last, emphasised at the beginning of her lecture that oral anticoagulants are rather new in clinical everyday life. This is a fragile and difficult-to-manage patient population. Up to 20% of all malignoma patients develop venous thromboembolism during the course of their treatment. And vice versa: About one fifth of all thrombosis patients have cancer. This can occur at the same time or be detected about six months after the onset of the thrombosis. The risk of venous thromboembolism is about five times higher in malignoma patients. There is a significant risk of recurrence of up to 21% per year and at the same time up to 12% of patients have an increased risk of severe bleeding per year. High vigilance is therefore required.
The invasively growing tumor takes advantage of blood clotting to invade the vascular system and continue to grow invasively through the vascular wall. Tumor cells hide in blood clots due to platelet activation and are thus not recognised by the defence system. As a result, haematogenous metastasis can take place.
Until 2019, low-molecular-weight heparins (LMWHs) were used as gold standard. Low-molecular-weight heparins vs vitamin K antagonists have been shown in studies to significantly reduce the risk of recurrent thrombosis within six months. For this reason, low-molecular-weight heparins were preferred for many years. However, the risk of severe bleeding within the first six months was very similar between the two drug groups.
It should be noted, however, that low-molecular-weight heparins, administered subcutaneously once or twice a day, are often stopped prematurely by patients. An evaluation of adherence over 6 months among 372 carcinoma patients with venous thromboembolism showed: Every 5th patient ended the therapy prematurely because of side effects - after a median of 90 days. Recurrent thrombosis occurred, including severe bleeding. The mortality rate was 28%.
In a recent study from the US, patients with cancer-associated thrombosis were compared according to how long they received DOAC or LMWH therapy. Only 34 days was the patient persistence with LMWHs compared to DOACs, which was 116 days.
The first large registration trial for cancer patients with venous thrombosis was published in 2018. Over 1,000 subjects were treated with either edoxaban or dalteparin (gold standard: 200 E/Kg per day for 1 month, then 150 E/Kg). Exciting result: Fewer recurrent thromboses in the edoxaban group. With regard to bleeding, however: More severe bleeding in the edoxaban group. These were mainly severe bleeding in the upper gastrointestinal tract in patients with gastrointestinal carcinoma. A second study compared rivaroxaban vs. dalteparin. The primary outcome was recurrent thrombosis and the safety outcome was severe bleeding. Again, the DOAC group showed significant reduction in recurrent thrombosis, while bleeding was more frequent in the rivaroxaban group.
The new Caravaggio study compared apixaban to LMHWs in 1,150 tumor patients. Again, there were fewer recurrences in the apixaban group than with dalteparin. All these trials were also designed to show non-inferiority of DOACs for recurrence rates, which was achieved. Regarding severe bleeding, no sign to the disadvantage of apixaban is seen, and no difference is seen for gastrointestinal bleeding.
Reference:
DGIM Congress 2021; Prof. Dr. Edelgard Lindhoff-Last (Frankfurt/Main): New therapies in everyday clinical practice