HHE Haematology supplement 2018 - Page 23

study outcome was the composite of recurrent symptomatic VTE and major bleeding complications (as assessed by an independent committee unaware of the study arm) occurring within 12 months of recruitment according to an intention-to-treat analysis (thus, irrespective of protocol violations and of drug discontinuation after the first six months). It is worth mentioning that patients randomised to edoxaban had, on average, one more month of anticoagulation compared with patients allocated to dalteparin. A similar proportion of patients allocated to the two study arms developed the main study outcome: 67/522 patients (13.8%) randomised to edoxaban and 71/524 (13.5%) allocated to dalteparin. Of interest, symptomatic recurrent VTE developed in 41 patients (7.9%) randomised to edoxaban and in 59 (11.3%) allocated to dalteparin; major bleeding complications developed in 36 (6.9%) and 21 (4.0%), respectively (not significant differences). Interestingly enough, severe bleeding complications (including fatal bleeding, intracranial, retroperitoneal or critical bleeding) developed in similar proportions (12 patients) in each of the two treatment groups. In addition, most major bleedings that developed in the edoxaban group were gastrointestinal bleedings in patients recruited because of gastrointestinal cancer. Also the rate of clinically symptomatic non-major bleeding was remarkably lower in patients treated with dalteparin (11.1%) than in those receiving edoxaban (14.6%). In a second smaller clinical trial, approximately 400 patients with a recent (either symptomatic or asymptomatic) CAT were randomised to receive from the beginning (without an initial parenteral treatment) either subcutaneous dalteparin (same schedule as the Hokusai/K) or oral rivaroxaban (15mg tid for the first three weeks, followed by 20mg oid thereafter) for six months. 15 The results of the Select/D study are consistent with those observed in the Hokusai/K. While the benefit–risk profile of the two drugs was found to be comparable, compared with dalteparin, rivaroxaban was associated with a remarkable reduction in the rate of symptomatic recurrent VTE (3.9% compared with 8.9%), and a substantial increase in the rate of major (5.4% vs 3.0%) as well as non-major clinically relevant (12.3% vs 3.0%) bleedings. Once again, the rate of severe bleeding was low in each of the study groups; and what accounted for the difference in the rate of major bleedings between edoxaban and dalteparin most was the occurrence of gastrointestinal bleedings in those cancer patients with gastrointestinal cancers who had been allocated to the edoxaban group. Conclusions According to the findings of the first two head-to-head comparisons between LMWH and the DOACs for the treatment of CAT, the following conclusions can be drawn: 1) the benefit – risk profile of the two drugs categories is comparable. As the novel drugs are less expensive and result in a considerable reduction in the burden and inconveniences for patients compared with LMWHs, their use in place of heparins is fully justified; 2) at least in patients who fulfil the recruitment criteria of the two clinical trials, the novel drugs are likely to be more effective; 3) they are associated with a higher haemorrhagic risk, particularly in patients with gastrointestinal cancer. In these patients, their use should be discouraged, as well as in patients who have problems with intake and absorption of oral drugs. Anyway, the risk of the most severe bleeding complications does not seem to differ between the two drug categories. In conclusion, an outstanding achievement has been obtained for the treatment of CAT, particularly desirable for patients who may require months or years of anticoagulation. 23 HHE 2018 | hospitalhealthcare.com References 1 Carrier M, Prandoni P. Controversies in the management of cancer- associated thrombosis. Expert Rev Hematol 2017;10:15–22. 2 Prandoni P et al. Cancer and venous thromboembolism. Lancet Oncol 2005;6:401–10. 3 Prandoni P et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002;100:3484–8. 4 Meyer G et al. Comparison of low molecular weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: A randomized controlled study. Arch Intern Med 2002;162:1729–35. 5 Lee AY et al. Low-molecular weight heparin versus a coumarin for the prevention of venous thromboembolism in patients with cancer. N Engl J Med 2003;349:146–53. 6 Hull RD et al. Long term low-molecular weight heparin versus usual care in proximal vein thrombosis in patients with cancer. Am J Med 2006;119: 1062–72. 7 Lee AY et al. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 2015;314:677–86. 8 Salter BS et al. Heparin- induced thrombocytopenia: a comprehensive clinical review. J Am Coll Cardiol 2016;67: 2519–32. 9 Gajic-Veljanoski O et al. Effects of long-term low-molecular- weight heparin on fractures and bone density in non-pregnant adults: a sy