Tag: Venous Thrombo Embolism

SUMMARY: XARELTO® (Rivaroxaban) is an oral, direct inhibitor of Factor Xa. Two previously published randomized studies concluded that XARELTO® was noninferior to the standard anticoagulation therapy (administration of heparin overlapped and followed by Vitamin K Antagonist), for most patients with Venous ThromboEmbolism. Further, XARELTO® in these studies also had a better safety profile compared to standard anticoagulant therapy. The authors in this pooled analysis combined the data from 2 identically designed studies, EINSTEIN-DVT and EINSTEIN-PE in which XARELTO® was compared to standard anticoagulation therapy, in patients with DVT and PE respectively. The goal of this study was to provide a more accurate estimate of the efficacy and safety of XARELTO® in elderly patients and cancer patients in whom Vitamin K Antagonists (VKA) such as COUMADIN® (Warfarin) can be associated with a higher complication rate. In addition, the study included analysis of outcomes with XARELTO® in patients with previous VTE and in those presenting with extensive thrombosis. Of the 8282 patients with VTE randomized in the pooled analysis, 4151 patients received XARELTO® and 4131 patients received LOVENOX® (Enoxaparin) / Vitamin K Antagonists. In both pooled studies, patients in the XARELTO® group received a dose of 15 mg PO BID for 21 days, followed by 20 mg PO QD whereas patients assigned to the standard anticoagulation therapy group received LOVENOX® subcutaneous at a dose of 1.0 mg/kg BID and either oral Warfarin or Acenocoumarol started within 48 hours after randomization and patients continued treatment for 3, 6, or 12 months, as determined by the local Health Care Providers. INR was closely monitored and maintained between 2-3. On final review, the analysis suggested that XARELTO® resulted in efficacy similar to standard anticoagulation therapy, with a noninferiority P<0.001. The pre-specified principal safety outcome was clinically relevant bleeding and major bleeding was observed in 40 patients belonging to the XARELTO® group and in 72 patients belonging to the standard anticoagulation therapy group (HR=0.54; P= 0.002). Similar benefits in the efficacy and safety were seen in the key subgroups evaluated, which included elderly fragile patients, cancer patients, patients presenting with extensive thrombosis and those with a history of recurrent VTE. The authors concluded that the incidence of major bleeding with XARELTO® was significantly less, particularly in the high risk group of patients, when compared to standard anticoagulation therapy and may therefore have a safety advantage, without compromising efficacy. Prins MH, Lensing AW, Bauersachs R, et al. Thrombosis Journal 2013;11:21

 

 

SUMMARY: The American Society of Clinical Oncology (ASCO) recently provided recommendations for the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer following a systematic review of 42 publications. They are as follows-

VTE prophylaxis in hospitalized patients

Majority of the hospitalized patients with active malignancy should receive VTE prophylaxis in the absence of contraindications. However there are no definitive data for VTE prophylaxis in patients admitted for short chemotherapy infusions, minor procedures or those undergoing stem-cell or bone marrow transplantation.

VTE prophylaxis in ambulatory patients

Routine VTE prophylaxis is not recommended although prophylaxis with low molecular-weight heparin can be considered in select group of outpatients with solid tumors who are receiving chemotherapy, after discussing the risk/benefits of such intervention. Patients with Myeloma receiving THALOMID® (Thalidomide) or REVLIMID® (Lenalidomide) should receive VTE prophylaxis with either aspirin or low molecular-weight heparin.

VTE prophylaxis in patients undergoing surgery

All cancer patients undergoing major surgical procedures should be considered for VTE prophylaxis with heparin unless there is a bleeding risk. This should be commenced preoperatively and can be complemented with mechanical methods to improve efficacy. This should be continued for at least 7-10 days and for up to 4 weeks postoperatively, in those undergoing major abdominal or pelvic surgery with restricted mobility, obesity, history of VTE or additional risk factors. Decision to consider prophylaxis, for patients undergoing low risk surgery, should be made on an individual basis.

Choice of Anticoagulation for cancer patients with VTE

For cancer patients who have a creatinine clearance of more than 30 ml/min and have newly diagnosed VTE , low molecular-weight heparin is preferred over unfractionated heparin for the initial 5 to 10 days. Low molecular-weight heparin, due to its superiority, is preferred over vitamin K antagonists for long term anticoagulation (6 months). Select cancer patients with metastatic disease or those receiving chemotherapy may be considered for anticoagulation with low molecular-weight heparin or vitamin K antagonists beyond the initial 6 months. A vena cava filter is indicated only for patients with contraindications to anticoagulant therapy and may be considered for those who progress despite optimal anticoagulation with low molecular-weight heparin. Patients with CNS malignancies and VTE should be anticoagulated like any other patient with VTE, monitoring closely for bleeding. Incidental VTE’s should be treated like symptomatic VTE. Decision to treat splanchnic or visceral vein thrombi diagnosed incidentally should be considered on an individual basis. The new novel oral anticoagulants are presently not recommended for prophylaxis or treatment of VTE.

Anticoagulation and survival benefit in patients without VTE

Cancer patients without VTE should not receive anticoagulants to improve survival, as there are no data to support this recommendation.

Predicting VTE in cancer patients using Risk Score

The risk score model below for VTE in cancer patients was developed and validated in multiple studies. The risk of VTE can be significantly reduced amongst these high risk patients by thromboprophylaxis
Lyman GH, Khorana AA, Kuderer NM, et al. J Clin Oncol 2013;31:2189-2204

 

 

 

 

SUMMARY: Apixaban (ELIQUIS®) is an oral, direct coagulation factor Xa inhibitor, similar to XARELTO® (Rivaroxaban). In this double blind study, ELIQUIS® was compared with conventional therapy, which included subcutaneous Enoxaparin (LOVENOX®) followed by Warfarin. Five thousand three hundred ninety five (5395) patients with acute deep vein thrombosis, pulmonary embolism or both, were randomly assigned to receive either ELIQUIS® 10 mg BID for one week followed by 5 mg BID for 6 months (n=2691) or conventional therapy with LOVENOX® followed by Warfarin (n=2704). The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death, related to venous thromboembolism. ELIQUIS® was non inferior to conventional therapy (P<0.001). The risk of major bleeding was slightly lower in the ELIQUIS® group. This efficacy and safety of ELIQUIS® was demonstrable in all patient subgroups. ELIQUIS®, similar to XARELTO®, will very likely be approved for the treatment of Venous ThromboEmbolism. Unlike Vitamin K antagonists (Warfarin), the newer oral anticoagulants do not require coagulation monitoring as they have a rapid onset of action, relatively stable pharmacokinetics and are not associated with significant drug interactions. It is important to realize however, that there are no agents presently available to reverse bleeding associated with these new oral anticoagulants. Development of antidotes that bind to factor Xa inhibitors, in order to reverse bleeding complications, are underway. Agnelli G, Buller HR, Cohen A, et al. N Engl J Med 2013; 369:799-808