Treatment Approach for DVT in Cancer Patients – Review
You have a patient with diagnosis of cancer and DVT and u need to start pharmacological anticoagulation. How will you approach ?
Treatment approach = Immediate anticoagulation (1-3 weeks) followed by continued anticoagulation (3-6 months)
Which drugs you will choose for Immediate anticoagulation ?
Either low molecular weight (LMW) heparin or a direct oral anticoagulant (DOAC) can be used.
Why not UFH?
LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. The evidence comes from a meta-analysis of 15 randomized controlled trials in cancer patients receiving anticoagulation for VTE (PMID: 29363105)
Is there any data to support use of DOAC for immediate treatment in cancer patients with DVT, as traditionaly UFH or LMWH were considered only options ?
Yes !!
[1] Apixaban Vs LMWH (dalteparin) in a RCT named CARAVAGGIO trial showed similar efficacy and bleeding rates.
[2] Rivaroxaban vs LMWH (daleparin) in pilot sudy (n = 406) SELECT-D showed similar efficacy but increased non major bleeding in patients with GI cancer in rivaroxaban treated patients.
So based on these data among DOACs, Apixaban has advantage of availability of RCT data so among DOAC apixaban can be prefered over rivaroxaban.
Continued Anticoagulation >> Continued use of the DOAC (apixaban or rivaroxaban) or LMW heparin can be done !!
Why not the cheaper warfarin ?
[1] Drug interactions, malnutrition and liver dysfunction can lead to wide fluctuations in INR. [2] RCTs (CLOT trial) and meta-analyses have shown superior efficacy of LMW heparin as compared with warfarin in patients with VTE in association with active cancer
NOTE >> For patients with renal insufficiency (eg, creatinine clearance <30 mL/min), in whom LMW heparin (and fondaparinux) is contraindicated and DOACs have not been investigated, intravenous unfractionated heparin (UFH) is preferred, although some experts administer renally-dosed enoxaparin with monitoring of antifactor Xa levels.
DOSING AND COST CALCULATION
NOTE > Dabigatran has not been studied in this population ie in patients with DVT/PE and malignancy so we haven’t discussed it here although it is approved and used and prophylaxis and treatment of DVT/PE in general.
NOTE >> Also look into weight based dosing in LMWH and follow changes as suggested in prescribing information for patients who are either underweight or overweight.
What about Platelet cutoffs for these drugs ?
Platelet counts >50,000/microL is not a contraindication whereas it is typically contraindicated in those with platelet counts <20,000/microL. For individuals with cancer and acute VTE who have platelet counts between 20,000 and 50,000/microL, the decision to anticoagulate should be individualized and based upon the risk of serious complications from VTE and the risk of bleeding associated with anticoagulation.
Among Dalteparin, enoxaparin, Apixaban and Rivaroxaban which of these you find most cost effective ?
Apixaban is available in india for price range 30-70 INR/5 mg tablet and so monthly cost for 5 BD would be 1800-4200/month and as it is oral so may be more preferable for long term treatment to your patient in comparison to LMWH which will cost a minimum of 10000/month for a 50-60 kg adult patient.
How will you administer enoxaparin ?
1.5 mg/kg SC once daily or 1 mg/kg SC twice daily (Upto 3-6 months). If you want to start oral ie DOAC start apixaban or rivaroxaban at continued anticoagulation doses only after minimum of 7 days of enoxaparin.
NOTE: Renally dosed enoxaparin (to be given when crcl <30 ml/min) – 1 mg/kg SC OD [ideally with monitoring of antifactor Xa Levels]
How will you administer dalteparin (LMWH) ?
200 international units IU/kg daily during month 1, then 150 IU/kg daily for months 2 to 6
What is dose for Rivaroxaban when it is started form 1st day ?
Rivaroxaban dose > Immediate anticoagulation by 15 mg twice daily for three weeks, then for continued anticoagulation with 20 mg once daily for (3-6 months)
What is dose for Apixaban when it is started form 1st day ?
Apixaban dose > Immidiate Anticoagulation by 10 mg BD X 7 days followed by continued anticoagulation by 5 mg BD X (3-6 months).
Apixaban (Eliquis) renal dosing: 5 mg BD dose can be reduced to 2.5 mg orally BD if at least one criterion is met: serum creatinine 1.5 mg per dL or more, age 80 years or older, or weight 60 kg or less. (Note: This dosing is based on trials for risk reduction of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and not on patients with DVT and cancer)
What if there is recurrent VTE with ongoing Anticoagulation ?
ISTH guidelines (Practice Point – Not based on RCT/Trail Evidence)
If on LMWH > Dose increase by 25% of current dose. If on DOAC then switch to LMWH
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