Transcatheter Aortic Valve Replacement and NOACs
Another area of interest for using NOACs is in the transcatheter aortic valve replacement (TAVR) population. This procedure was developed for those with severe aortic stenosis as an option instead of open aortic valve replacement surgery. There is a continued need for optimal antithrombotic regimens and there is an ongoing clinical trial to evaluate this.
Current guidelines recommend 3 to 6 months of DAPT (dual antiplatelet therapy) with aspirin plus a P2Y12 inhibitor following TAVR. If a patient has a preexisting indication for oral anticoagulation use, such as atrial fibrillation, they should continue taking the same anticoagulant following TAVR. The rationale for this strategy is twofold. The first is to protect against device-related thromboembolic events while endothelialization of the metallic catheter valve frame is occurring.27 The second is to decrease the incidence of bioprosthetic valve thrombosis and subclinical thrombosis. Consideration should be given to the benefits vs the bleeding risk. If the bleeding risk is high, then single antiplatelet therapy would be indicated.
Multiple clinical trials are investigating the efficacy and safety profiles of dual antiplatelet vs single antiplatelet vs oral anticoagulants in patients with TAVR. The use of oral anticoagulant therapy has been shown to prevent the development of both clinical valve thrombosis and subclinical leaflet thrombosis without increased bleeding in comparison to antiplatelet therapy. Clinical trials are presently investigating the use of apixaban, edoxaban, and rivaroxaban.28
NOAC Therapy in Oncology
Most recently, clinical trials are ongoing evaluating NOACs, particularly rivaroxaban and apixaban, for the use in thromboprophylaxis in ambulatory cancer patients and in patients with metastatic disease undergoing chemotherapy.39,30 The National Comprehensive Cancer Network (NCCN) guidelines for patients with cancer who are considered at high risk for VTE recommend thromboprophylaxis with unfractionated heparin (UFH), LMWH, or fondaparinux. Unfractionated heparin and LMWH both inactivate factor Xa by improving the action of antithrombin.30 Unfractionated heparin is predominantly metabolized by the liver but there are no significant dose adjustments. LMWH is metabolized by the kidneys so renal impairment may affect excretion and may require dosing considerations. Fondaparinux is a factor Xa inhibitor metabolized by the kidney; thus, dose adjustment may be needed for renal impairment.31 The recommendations for surgical cancer patient who are at high risk is the same.
The Khorana scoring system (Table 5) is used for ambulatory medical oncology patients to determine risk.32 For intermediate-risk patients with a score greater than or equal to 2, prophylaxis is considered using apixaban or rivaroxaban for 6 months.
Table 5. Khorana Scoring System32
|Prechemotherapy PLT count ≥350 × 109/L||+1|
|Hemoglobin level <10 g/L||+1|
|Prechemotherapy leukocyte count >11 × 109/L||+1|
Table adapted from Mulder et al.32
Patients with multiple myeloma are risk-stratified using the SAVED or IMPEDE scoring system. The SAVED score is based on the following criteria: a history of previous surgery, Asian race, VTE history, age 80 years or older, and dexamethasone dose. The researchers found that this model stratified about 30% of patients as at high risk for VTE.33
The IMPEDE score is based on immunomodulatory agent, BMI greater than or equal to 25, pelvic or femur fracture, erythropoietin stimulating agent, dexamethasone/doxorubicin, Asian ethnicity, VTE history, tunneled catheter/central line, and existing thromboprophylaxis.34 Those with a SAVED score greater than or equal to 2 or IMPEDE score greater than or equal to 3, warfarin or LMWH are used. For patients with SAVED score less than 2 or IMPEDE score less than 3, clinician should consider apixaban or aspirin therapy.35
Specific criteria are used for patients with and without gastric/gastroesophageal lesions.31 For patients without gastric/gastroesophageal lesions, apixaban is preferred over rivaroxaban for thromboprophylaxis. For patients with gastric/gastroesophageal lesions, dalteparin is preferred over enoxaparin. Preferred combination therapy options for patients without gastric/gastroesophageal lesions include edoxaban plus LMWH/UFH or LMWH/UFH for 5 days, followed by edoxaban. If this therapy cannot be used, the dabigatran plus LMWH/UFH can be used for 5 days, followed by dabigatran.31 A third option may include warfarin plus LMWH/fondaparinux/UFH until INR reaches greater than or equal to 2.0, then continue with warfarin alone.36
Reversal of NOAC Action
With the development of NOACs, there became a concern surrounding the ability to reverse these agents in a bleeding emergency. Reversal agents have been developed for patients taking NOACs who need urgent surgery or who have life-threatening bleeding. Idarucizumab is a reversal agent for the direct thrombin inhibitor dabigatran.37 This agent is a monoclonal antibody fragment that is given intravenously as a 1-time dose. The reversal agent for the factor Xa inhibitors (apixaban, and rivaroxaban) is coagulation factor Xa (recombinant), which is a modified human factor Xa protein given as a 1-time intravenous bolus or infusion. It is not indicated for the reversal of edoxaban.38
Over the past decade with the development of NOACs, numerous changes and advances have been made in treating and preventing stroke related to atrial fibrillation, DVT, and PE treatment and prophylaxis; CAD risk reduction; and thromboprophylaxis in cancer patients. Practitioners should be aware of new recommendations regarding NOACs and also the importance of proper dosing for each population. Due to the complexity of dosing based on condition, renal function, age, weight, and bleeding risk, the practitioner must be extremely vigilant to assure patient safety and appropriate dosing. As more clinical trials and data become available, the expanded use of NOAC use will continue.
Barbara Bentz, RN, MSN, CRNP, is an instructor of medicine in the Heart and Vascular Institute at Penn State Health, specializing in electrophysiology. Denise Rhodes, MSN, CRNP, FNP-BC, is an instructor of medicine in the Heart and Vascular Institute at Penn State Health, specializing in interventional cardiology and structural heart disease.
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