HHE Haematology supplement 2018 - Page 22

haematology and oncology Perspectives for treating cancer-associated thrombosis Fixed-dose treatment with the novel direct oral anticoagulants is likely to replace subcutaneous low-molecular-weight heparins for most cancer patients with venous thromboembolism Paolo Prandoni MD PhD Andrea Piccioli MD PhD Arianna Foundation on Anticoagulation, Bologna, Italy It is well known that patients with cancer- associated thrombosis (CAT) have a risk of both venous and arterial thrombotic complications, which exceeds by far that expected in the general population. 1 These vascular complications prevail in patients with the most advanced stages of cancer, and are often life-threatening. 1 Indeed, pulmonary embolism (PE) is the second most common cause of death in patients with CAT, soon after mortality induced by cancer itself. 1 Although venous thromboembolism (VTE) is often triggered by identifiable risk factors (such as surgical operations, central or peripheral venous catheters, chemotherapy or long-standing immobilisation) either alone or in various combinations, VTE complications often arise spontaneously, making it virtually impossible to either predict or prevent their development. 2 Conventional treatment When VTE episodes develop in patients with cancer, they are often resistant to conventional treatment. It has, indeed, been shown conclusively that the rate of symptomatic recurrent VTE in CAT while on (even correct) treatment with vitamin K antagonists (VKA) exceeds that expected in patients without cancer by 3–4-times. 3 Unfortunately, the rate of major bleeding complications increases as well, making increasing the intensity of VKA therapy unsuitable. 3 Low-molecular weight heparins A number of randomised clinical trials, performed in the last ten years, have conclusively demonstrated that the initial and long-term treatment of CAT with therapeutic or slightly sub-therapeutic subcutaneous doses of low- molecular weight heparins (LMWHs) is associated with a statistically significant and clinically relevant reduction in the risk of subsequent symptomatic recurrent VTE over VKA with a comparable risk of major bleeding. 1,4–7 Their use, however, leads to a considerable burden for patients and a considerable cost for health care systems. They are, indeed, much more expensive than both the older and the novel oral anticoagulants, so that in many both European and non-European countries they are not reimbursed beyond the first weeks of therapy. Moreover, they are not free from inconveniences, including heparin-induced thrombocytopenia, 8 which makes monitoring 22 HHE 2018 | hospitalhealthcare.com of the platelet count at least in the first two weeks mandatory, and the long-term development of osteoporosis and spontaneous fractures. 9 Finally, the absolute rate or recurrent symptomatic VTE complications occurring while on LMWH therapy (ranging between 7% and 9% in the available randomised clinical trials) exceeds by far that observed in non-cancer patients (1.5 – 3%) while on conventional anticoagulant treatment. 1,4–7 This risk has been reported to persist beyond the first six months of treatment, and has been found to be associated with an increasingly high risk of major bleeding complications. 10,11 Interestingly enough, in a prospective cohort study dealing with the six-month observation of approximately 400 consecutive patients with active cancer and a recent episode of VTE who had been given therapeutic doses of LMWH, the cumulative incidence of heparin discontinuation because of either recurrent VTE or major bleeding was approximately 20% of all patients. 12 In conclusion, LMWHs have become the treatment of choice for patients with CAT because of an evident superiority over VKA, but the benefit – risk profile of their administration is far from being optimal. Novel direct oral anticoagulants Following the demonstration that in subgroups of patients of cancer the novel direct oral anticoagulants (DOAC) possess a favourable benefit–risk profile in comparison to conventional anticoagulation for the trea Y[وX]BK LH\[وH\XY ]XY\\\ۜ]Y[U[P]BX[HY[X\Y M[[[[X[ [Z\Y[X[X[Y\[HۋZ[\[ܚ]HوYX[Hݙ[[X]܈وX܈JH\\Y]U܈HX]Y[وU  L ]Y[]X]H[\[HX[\\Hق[\X]X܈\[\X]XH\H][]X\]H^\و\[\[X]Y[]U܈ۙ\\[^ [\H[[Z\YXZ]HZ]\X][[\™[\\[ UK܈ۙH[۝YBMLUKH܈ܘ[YX[ YY [Y[]Y[][\]H[[Z[\KBZY܈ۘZ][X]Y[]ۙš[X]ܜو YXZ[H܈]X\^[۝ˈ MH۝[X][ۈوHX]Y[^[ۙH\^[۝\YB\ܙ][ۈوHYH\]ܜˈHXZ[