Table 2: Overview of Phase III trials of NOACs in the acute treatment of VTE
Dabigatran Trial Comparator
Single drug regimen
RE-COVER RE-COVER II
No, initial treatment with LMWH
Number of patients 5132 Dose
150mg BID Treatment duration Six months
Initial UFH/LMWH pretreatment
Recurrent VTE NOAC/comparator
Major bleeding NOAC/comparator
Mandatory (≥five days)
EINSTEIN DVT EINSTEIN PE
Enoxaparin/VKA Enoxaparin/VKA VKA Yes
15mg BID (three weeks)/20mg bid
10mg BID (one week)/5mg bid
3, 6 or 12 months Six months
Mandatory (48 hours) for comparator group
Not recorded None
initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004;140(11):867–73.
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No, initial treatment with LMWH
8240 60mg OD
Flexible, up to 12 months
Mandatory (at least 5 days
30mg OD (*)
VKA: vitamin K antagonist, LMWH: low-molecular weight heparin, UFH: unfractionated heparin, eGFR: estimated glomerular filtration rate, NOAC: new oral anticoagulant drug, P-gp: P-glycoprotein, CYP3A4: cytochrome p450 3A4 (*) Dose reduction for low body weight ≤60 kg; concomitant use of P-glycoprotein (P-gp) inhibitors (ciclosporin, dronedarone, erythromycin, or ketoconazole); or moderate to severe renal impairment (CrCl 15– 50ml/min)
coagulation can prevent VTE and reduce morbidity and mortality in established VTE, but potentially increase the risk of bleeding. The balance between optimal efficacy and maximal safety has fuelled the search for new anticoagulant drugs. While LMWHs provide predictable pharmacokinetics and a rapid and reliable anticoagulant effect, their use is limited by the need for injection. On the other hand, oral VKAs have a slow onset of action. Due to their narrow therapeutic index and their unpredictable and highly variable anticoagulant effect, continuous monitoring of VKAs is mandatory. This routine testing adds cost to the health care system but, more importantly, is inconvenient for patients and physicians. To overcome the inconveniences of VKA therapy, a new generation of non-VKA oral anticoagulants has been developed. Efficacy and safety of NOACs for the prevention (edoxaban is not indicated for primary prevention) and treatment of VTE have been established and they are likely to become the treatment of choice for the majority of patients. l
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